OCT and FA in Diagnosing and Managing Diabetic Eye Disease
A panel of specialists explain how they utilize both tools in practice.
KEITH CROES, ELLEN KUREK

The Retinal Physician Editorial Advisory and Review Board developed a number of questions regarding the use of optical coherence tomography (OCT) and fluorescein angiography (FA) in the management of diabetic eye disease. We posed those questions to a panel of retina specialists. Their responses are summarized here.

Will OCT replace FA in the diagnosis and management of diabetic eye disease?

The panel unanimously agrees that OCT cannot replace -- but complements -- FA and clinical examination in the diagnosis and management of diabetic eye disease.

"I don't think OCT has replaced FA," says Emily Chew, MD, deputy director of the Division of Epidemiology and Clinical Research at the National Eye Institute (NEI), Bethesda, Md. "The clinical exam and the fluorescein angiogram are still very important in the diagnosis and management of diabetic macular edema (DME)."

"OCT is a great tool to see if there is retinal thickening, and FA provides information about where the leakage is coming from," Rick Ferris, MD, of the NEI, points out. "They are complementary. There is better information on the OCT regarding the degree of retinal thickening, even if the FA is done in stereo, and there is much better information about [identifying] the source of leakage using FA."

Although the availability of OCT has stimulated expanded use of intravitreal steroids, the results of this treatment approach do not appear to justify its use as first-line therapy. "The first line of treatment at this point is still laser therapy, even though there are a lot of steroid injections being done," Dr. Chew says. "If you're of that camp, you may argue that if you look and see leakage, you just inject intravitreal steroids. But the fluorescein angiogram is still important when you are thinking about treating the patient (with laser therapy)."

"The fact that there is a number to put on the thickness of the retina has led to the increasing popularity of intravitreal steroids for DME," Dr. Ferris notes. However, he continues, "The reduction in retinal thickening seen on OCT is much more impressive than the visual acuity response."

George Sharuk, MD, retina specialist and clinical researcher at the Joslin Diabetes Center, an affiliate of Harvard Medical School, says he's conservative when it comes to performing FA. "I generally reserve fluorescein angiography to direct my treatment for DME," he says. "The important factor for diagnosis is a careful, stereoscopic evaluation of the retina and macula using slit-lamp biomicroscopy. You can see most of the pathology just by doing a thorough examination." However, once he has diagnosed clinically significant macular edema according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) criteria based on the stereoscopic examination, Dr. Sharuk takes 7 standard-field stereo color photos and performs FA unless there are contraindications, for example, if the patient is allergic to fluorescein. The angiogram enables him to determine whether the patient has treatable lesions based on ETDRS definitions. He also does OCT at baseline to be able to document the topography and amount of retina thickening and to follow the response to treatment over time.

"The OCT does not really tell me how to treat these patients," Dr. Sharuk says. "It is not geared to looking into the sources of leakage, although there are some clues that you can see on the OCT regarding certain characteristics of diffuse versus focal leaks. For example, cystoid macular edema (CME) is more typical of diffuse leakage, and the OCT can help characterize the edema."

According to Dr. Sharuk, "These are two different tests that look at two different things. Each test adds different information." Whereas OCT documents the presence of macular edema, FA outlines the retinal blood vessels, Dr. Sharuk notes. FA also differentiates between focal and diffuse leakage, which has important treatment implications. "Fluorescein angiography identifies what we call treatable lesions -- focal leaks. According to the ETDRS recommendations, focal leaks are treated focally, and areas of nonperfusion and diffuse leakage are treated with grid treatments," he says. He adds that FA also can be used to find evidence of foveal nonperfusion that has prognostic value in determining potential improvement in visual acuity.

"The major significance of OCT is that it quantitates leakage, whereas before with fluorescein alone you couldn't quantitate the leakage: it was a qualitative evaluation," says retina specialist Mark Nelson, MD, of Winston-Salem, NC. "And most importantly, if you treat somebody, you can actually see the changes, week by week, month by month," Dr. Nelson adds.

Figure. The OCT scan on this patient showed cystoid macular edema with foveal thickening to 326 microns, an inferotemporal area of moderate retinal thickening, and milder thickening nasally and superiorly. The fluorescein angiography on this patient (not shown) showed late microaneurysmal leakage corresponding to the areas of retinal thickening appreciated on the OCT. Source: Mark Nelson, MD.

In what cases of diabetic eye disease is OCT the most helpful to you and why?

According to the panel, the primary role of OCT is in documenting and quantitating the extent, location, and severity of DME and how it responds to treatment. "Although it sometimes may not be as reproducible as you'd like, OCT gives you an objective measurement of macular thickness," Dr. Chew explains. "Speaking as someone who does clinical trials, it's nice to have the actual measurement before and after treatment. I think that its usefulness is in showing what happens over time."

According to Dr. Nelson, longitudinal OCT measurements are particularly important in deciding whether additional laser treatments are needed after initial laser therapy. "It really helps you make decisions on how you're going to treat a patient. If you give somebody laser therapy and the leakage is decreasing at each follow-up visit, you wouldn't think about doing another laser treatment while the patient is still improving," he notes.

The retina specialists interviewed also point out that because OCT sheds particular light on the vitreoretinal interface, OCT also helps to identify vitreous traction on the retina or macula. Dr. Nelson notes that such traction can be difficult to see on FA or clinical examination and has important implications for treatment. "If somebody is not responding to laser therapy and you see vitreous traction, you know they have a surgical disease as opposed to a disease that could be treated with laser therapy or intravitreal steroids," he says. "Many, many times I've operated on people I never would have dreamed of operating on because the OCT showed me that surgery (vitrectomy) would help because there was vitreous traction."

Dr. Nelson also notes that OCT can be useful in identifying other factors that contribute to eye disease in diabetic patients, such as epiretinal membrane or macular degeneration. "We see a lot of patients who have macular degeneration and diabetic retinopathy. Just because they're diabetic doesn't necessarily mean that's what the problem is."

In what cases do you use OCT in place of FA? And what do you use it to determine?

None of the panelists use OCT in place of FA at the initial examination. However, some use OCT alone to follow up previously laser-treated patients to determine whether additional laser treatment may be indicated. "I am sure that there are times when the sites of leakage are known and OCT is all that is needed [along with the eye exam] to determine the effect of previous treatments and the necessity for additional treatments," Dr. Ferris says.

"The only time that I ever use OCT by itself is in postoperative patients," Dr. Nelson explains. "If somebody has macular leakage, macular edema, and I do macular laser therapy on them, I would do OCT on follow-up. I wouldn't do another fluorescein -- there's no reason to."

Dr. Chew reports, "It's possible that I would perform an OCT if I've treated the patient and it looks like it might be a little better but I'm not certain I'm going to treat it again. But it doesn't replace a fluorescein angiogram. It may just give me added information at a visit when I normally wouldn't do a fluorescein angiogram."

In what cases do you use FA only, and not OCT? Why?

The panel agrees that they seldom or never perform FA without OCT. "I don't use fluorescein instead of OCT because they are two different tests and one does not replace the other in any way," Dr. Sharuk observes. Dr. Nelson adds, "The only time I would do fluorescein only is if I were looking for nonperfusion or causes of proliferative diabetic retinopathy. But that's in the periphery, not in the macula. If I suspect a macular process, I always do an OCT."

According to Dr. Chew, "I get a fluorescein angiogram and not necessarily an OCT when I think the patient clinically has edema and I'm going to do treatment. But by and large I would get an OCT as well because usually our patients are in some sort of research protocol. But that OCT isn't always necessary."

In what cases are OCT and FA complementary? What does each tell you in these cases and how do you make use of both sets of test results?

The panel concurs that OCT and FA are always complementary. "They're totally complementary," Dr. Chew says. Dr. Nelson agrees, "They in no way really replace each other."

As Dr. Chew explains, "The fluorescein shows where the leakage may be, but leakage doesn't always mean thickening. If you do see thickening, that helps establish if that leakage is really important. Alternatively, if they're showing that there's minimal leakage and there's little edema, that's useful. So the two of them always complement each other."

"You can get an idea of what quadrant the leakage is in from looking at the OCT mapping," Dr. Nelson says. "But the fluorescein will tell you specifically where in the retina or macula the leakage is coming from and also will tell you if the leakage is microaneurysmal or nonmicroaneurysmal. You can't tell that from the OCT." (Figure)

However, according to Dr. Nelson, in some cases OCT provides information on the source of leakage that is difficult to obtain from FA. "In the old days, we would do 3-dimensional viewing of the fluorescein angiogram to determine whether the leakage was subretinal or sub-RPE [retinal pigment epithelium] or intraretinal. The OCT takes away that guesswork and tells you specifically what level the leakage is coming from," he says.

Dr. Nelson adds that a fluorescein angiogram can also serve as a useful orientation tool. "A lot of times I'll do a fluorescein just to have a roadmap of where the fovea is before I do a laser treatment. The OCT doesn't show you that."

What type of quantitative analyses do you perform? What measurement of thickness do you find the most useful?

Foveal thickness is the most important thickness measurement for Dr. Nelson because it correlates with the presence or absence of CME in the fovea, which in turn corresponds with visual acuity. The second most important quantitative analysis for him is the comparison of whether the area of retinal thickening has increased or decreased between 2 time points. According to Dr. Nelson, this measurement "always corresponds beautifully with vision, so it's a very powerful, sensitive tool." However, he points out, "You have to realize it's a logarithm and it's based on the ability of the photographer to take the pictures. But if you know how to look at it, it's really helpful."

Another important OCT test result for Dr. Nelson is the color map of retinal thickness and volume, a qualitative result that shows the location of the thickening. "The map automatically tells you whether these people qualify for macular laser from that one view," he notes. "Some people just treat because there's leakage there. But if you go by the original ETDRS study, which is based on retinal thickening, the OCT is perfect because it shows that there are areas of retinal thickening. In the old days, if you had a fluorescein angiogram, you could see the leakage, but if the body can reabsorb that leakage and it doesn't swell up, by definition it doesn't really benefit from laser. So then you had to look in the eye to see if the macula was thickened, and that's hard for some people. With OCT, it's a no-brainer."

In addition to using other findings, Dr. Sharuk relies on 6 radial OCT views, or "cuts," as well as the computer-generated topographic map of the macular area. He concurs with Dr. Nelson that "the most important measurement of thickness is the central area, which to me is a measurement of the involvement of the fovea. That's very important because macular edema affects visual acuity when the center is involved. When it's outside the center it at least does not cause visual loss, although it might cause some other symptoms like distortion."

Dr. Sharuk adds that even when OCT shows no abnormal macular thickening, close examination of the radial cuts often shows cystic changes in the fovea that signal macular edema. "So I look at both the topography and the thickening as well as the anatomical changes," he explains. "An important thing that I look at besides the quantitative aspect is also the quality of the vitreoretinal interface, the presence or absence of vitreomacular traction. This is not a thickness measurement. It is actual anatomical information that we get from the OCT."

Dr. Chew says that she does vertical cuts as well as radial cuts and often hand-calibrates areas of particular interest during follow-up exams. She explains that she's interested in the whole retina, not just the central fovea, and can often get a good "gestalt" just by looking at the eye unassisted.

Do you use OCT solely as a yes/no tool for identifying the presence or absence of edema?

None of the specialists who replied to our questions uses OCT merely as a tool for identifying the presence or absence of macular edema. "It's a great screening tool, but then you have to dive into it a little bit more so that you can get more information out of it," Dr. Nelson explains. "I go through the whole series of OCT pictures to look at the areas of leakage and whether the vitreous or something else is influencing them. That's what I love about the machine. If you're looking for answers it gives you answers. If you're not looking for answers, it's a quick, easy test. But as a retina specialist you're constantly looking at where there's leakage and where it's coming from. Do they just need laser therapy, or do they need surgery? There are all these different questions that have to be answered if you want to be successful. So it's great to be able to increase the success rate of my procedures because I know exactly what to do now. I don't waste my time on laser therapy if I know it's a surgical disease."

Like Dr. Chew, Dr. Sharuk relies on the results of clinical examination rather than on OCT to identify macular edema, and uses OCT as a follow-up tool. Nevertheless, he acknowledges that those who are not retina specialists might find OCT helpful in indicating the possible presence of macular edema that would require confirmation through thorough examination. However, he notes that the manufacturer of the Stratus OCT instrument, Carl Zeiss Meditec, upgraded the software in June to include normative data on retina thickness. This upgrade enables the instrument to compare the thickness of the retina being imaged with the thicknesses stored in the normative database. Thus, Dr. Sharuk explains, "The OCT might show some retinal thickening that you might not see on the exam." However, he adds, "We don't know the significance of so-called subclinical diabetic macular edema based purely on OCT results. The DRCR (Diabetic Retinopathy Clinical Research) Network is considering a study to evaluate this significance."

The physicians interviewed for this article reported that they have no financial interest in the Stratus OCT instrument and no financial relationship with Carl Zeiss Meditec.