While dilation and fundus photography are the mainstays of diagnosing vision-threatening complications from diabetes early on, problems arent always readily apparent.
Consider this patient who recently presented to optometrist Joe DeLoachs Plano, Texas, practice. A 45-year-old white female with a 20-year history of type 1 diabetes complained of dimness in her vision. Visual acuity was 20/20 O.U. at distance and near, refraction remained stable, and the slit lamp and dilated fundus examinations were unremarkable.
Retinal mapping, however, showed a slight thickening, indicating that she had mild diabetic macular edema. Dr. DeLoach instructed the patient to return for a repeat retinal thickness analysis in three months, and plans to refer her to a retinal specialist for laser treatment if the edema appears to progress. With her excellent acuity and normal clinical picture, this would be one of those cases where you would have missed the slight macular edema, he says.
With advances in technology for mapping the retina, a diagnosis such as Dr. DeLoachs is less likely to be missed. Thats good news given that 12,000-24,000 people who go blind from diabetic retinopathy each year.1 Here, well look at what you can learn from retinal maps.
Least Apparent Problem
Diabetic macular edema and proliferative diabetic retinopathy pose the most significant threats to vision in diabetic patients.
An abnormal accumulation of fluid in the retinal tissue characterizes macular edema, which explains the accompanying increase in retinal thickness.2 The Early Treatment Diabetic Retinopathy Study (ETDRS) labels macular edema as clinically significant if you observe retinal thickening or hard exudate associated with adjacent retinal thickening within 500 microns of the center of the foveal avascular zone.3 According to EDTRS, however, diabetic macular edema is successfully treated with laser photocoagulation.
Problem is, diabetic macular edema is also one of the hardest conditions to detect. You can have zero to minimal compromise of visual acuity and still have macular edema, says Louisville, Ky., optometrist Larry Alexander.
Indeed, researchers have confirmed that retinal thickening from diabetic macular edema is not associated with the presence of clinically visible pathology. This finding, they say, is proof of the necessity to assess retinal thickness in order to diagnose diabetic macular edema.4 Though such methods as stereophotography, slit-lamp biomicroscopy and fluorescein angiography are useful in identifying many cases, even they are not always able to detect diabetic edema early on. Consider these results of one study:4
- Slit-lamp biomicroscopy missed small amounts of thickening (1.5 times above normal). In other instances, slit lamp examination led clinicians to overestimate the size of the thickened area.
- Stereophotography did not identify locations with mild or localized thickening. Also, doctors base grading on local differences rather than comparisons with normal values, thus hindering the detection of diffuse edema.
- With fluorescein angiography, 96% of the locations with twice the normal amount of thickness depicted fluorescein leakage outside the fovea. However, appreciable fluid accumulation did not always accompany this, as demonstrated by fluorescein leakage at 72% of the sites with normal retinal thickness.
Hence, theres the need for a method to measure the amount of retinal thickening in order to identify patients with diabetic macular edema early on, and to evaluate the effectiveness of treatment.6
One such instrument designed to address this need is the Retinal Thickness Analyzer (RTA) from Talia Technology Ltd. Talia first introduced the RTA overseas in 1991 and in the United States in 1997.
Originally listed at $90,000, the technology was beyond reach of most optometric practices. The list price has since dropped to $57,800, and special programs are available. Talia also has introduced a second-generation version of the RTA that is more compact and automated, making the technology more practical for O.D.s offices.
This 3-D, multi-purpose system combines a fundus camera and computerized scanning slit lamp to measure retinal thickness between the internal limiting membrane and the retinal pigment epithelium, where 50-60% of the ganglion cells are. The registration software and high reproducibility of the system makes it very effective in picking up very small and subtle changes in thickness and thinning, Talia spokeswoman Kathleen Hand says.
The test is non-invasive and takes 3-4 minutes per eye. Using a narrow slit of green helium-neon laser light and digital camera, the RTA takes five 3-by-3mm scans of the retina, starting at the center of the fovea, followed by the upper right and left, and lower right and left portions. With the fundus image and blood vessels as a guide for accuracy and repeatability, it overlays each scan for an overall 6-by-6mm scan.
The RTAs computerized algorithm analyzes optical cross-sections and provides registered thickness maps and comparative reports, including disc topography. The instrument compares to a comprehensive database showing a color scale. Cooler colors show a thinner area, while warmer colors show thickening of edematous layers. The RTA gives specific measurements in microns at each of 1,280 data points.
Dr. DeLoach considers the RTAs versatility to be its chief advantage. Because it takes measurements at several different portions, clinicians can use it to diagnose glaucoma, diabetic retinopathy and maculopathy. And, he says, it shows ischemic changes in the nerve fiber layer.
One disadvantage of this device: Media opacities may affect results. If you have extensive lens changes, the quality of your imaging does decline, Dr. DeLoach says. If you have advanced lens changes, you really just dont get acceptable images that are clinically useful, he says.
Several studies have demonstrated the ability of the RTA to measure retinal thickness in comparison with biomicroscopy. Researchers using the RTA were able to quantify retinal thickness in a patient with diabetic macular edema, documenting that the retina was 1.7 times the normal thickness.6
In a Japanese study of 35 patients with diabetic retinopathy, the RTA detected abnormal foveal thickness in nine eyes in which biomicroscopy would have missed this finding. The RTA also detected abnormal thickening in eyes that appeared normal on fluorescein angiography.7
A Coherent Approach
The Optical Coherence Tomographer (OCT) from Zeiss Humphrey Systems works like a B-scan ultrasound to provide cross-sectional images of the retina. It allows you to see the anatomy of the macula at a 10-20 micron resolution. Once used primarily in university settings by retinal and glaucoma specialists, the OCT now has garnered more interest among private practitioners, especially since the release of a smaller version, the OCT2, last October.
This non-contact device takes six, 6mm scans in a clock-type motion (12-6 oclock, 1-7 oclock, etc.) to account for normal variations in thickness of different portions of the macula. One disadvantage is the scan takes about 10 minutes for both eyes, depending on patient cooperation. The patient must be dilated, so allow for additional time.
The OCT software offers volumetric analysis (and nerve fiber layer analysis for glaucoma suspects). It then compares the scans to a normative database of 1,200 eyes to show whether the patient falls outside normal levels. (Zeiss Humphrey plans to introduce an updated software package that will include age-matched reference data.) OCT also provides 3-D maps to show portions of the macula that are too thick or thin. Rick Torney, OCT business manager for Zeiss Humphrey, believes that the OCT may show differences in thickness at least six months before they would become apparent on fundus photography or fluorescein angiography.
As with the RTA, research shows the OCTs ability for detecting macular thickening early on. One study of 102 patients (182 eyes) found that the OCT and biomicroscopy almost always correlated, but that in some instances the OCT detected thickening when biomicroscopy did not. The OCT also correlated with regions of fluorescein leakage, and occasionally revealed thickening in the absence of leakage.8
Other studies correlate with these results. Some examples:
- Using OCT, researchers in Taiwan identified cystoid macular edema in 11 of 19 eyes without evidence of clinically significant macular edema (58%) and 12 of 14 eyes with evidence of CSME (86%).9
- German researchers used OCT and found significant differences in retinal thickness between the 45 diabetic patients without CSME and 25 healthy subjects with CSME. The differences were especially significant in the macula, at the foveal rim, and in the nasal and superior hemispheres.10
- The OCT and RTA were in agreement with retinal thickness measurements and in identifying eyes with significant thickening, according to a presentation at this years meeting of the Association for Research in Vision and Ophthalmology (ARVO).11
The Heidelberg Retina Tomograph, a scanning laser ophthalmoscope, takes 32 images at different focal planes to construct a 3-D model of the optic nerve. Once primarily used for detecting glaucoma, the device also can aid in the diagnosis of diabetic macular edema.
One study found that the HRT offered reproducible measurements in diabetic eyes, and may be useful for quantifying diabetic macular edema and monitoring the effectiveness of laser therapy.12
Another study at this years ARVO meeting compared HRTs maps with clinical assessment of retinal thickening in 19 patients with progressing diabetic macular edema. Sixteen converted to clinically significant DME, 13 of whom did so within nine months from baseline. The HRT, however, detected a significant increase in the edema index in 15 of these 16 patients, typically up to the clinical conversion. While the study is ongoing, the researchers believe the HRT can be useful for quantifying retinal edema.13
Mapping Out Change
All three mapping techniques not only allow for earlier detection of diabetic macular edema but also allow you to monitor changes in patients over time, gauge the effectiveness of treatment and determine whether further treatment is necessary. That may be [one of the] most important uses, Mr. Torney says.
Researchers from Tufts University School of Medicine in Boston studied four patients (five eyes) who underwent laser photocoagulation for CSME secondary to diabetes; the procedure was specific to areas of retinal thickening detected by OCT and clinical exam. A follow-up OCT showed an early positive response to focal laser treatment.14
Also, researchers from the University of Illinois at Chicago used the RTA to compare retinal thickness measurements in 20 patients with diabetic macular edema before and after focal laser treatment. They found that the level of foveal thickening before treatment strongly correlated with the results of treatment. Specifically, eyes that were about 1.6 times the normal foveal thickness (60% thickening) had a nearly 50% probability for reversal of thickening to within the normal range, while eyes with thickness more than 2.8 times above the normal level had a less than 2.5% probability of reversal.15
A New View
New on the retinal mapping scene is the Retinal Function Imager (RFI) from Optical Imaging Ltd. of Rehovot, Israel. Clinical trials are under way in the United States, and the company hopes to obtain 510K FDA clearance next year.
The RFI allows for non-invasive imaging of the retina. Images include retinal blood flow-rate (including in the smallest capillaries), oxygen saturation maps and functional maps of retinal metabolism in response to photic stimulation. Each has relevance to basic issues in retinal physiology and to clinical issues in diabetic retinopathy, glaucoma, age-related macular degeneration (AMD) and other retinal disorders, the company says. Besides these non-invasive images, the RFA can serve as a digital fundus camera for fluorescein and ICG angiography.
One company-funded study looked at the following:16
- Blood flow. Movies of retinal blood flow showed that the flow was slower in diabetic patients than it was in healthy subjects.
- Oximetric state. An oximetric map disclosed areas of low oximetric state that correlated to the area of nonperfusion on fluorescein angiography.
- Metabolic signal. Normal subjects demonstrated functional response of the retina to light stimulation, beginning approximately 1 second after stimulation, peaking at 4 seconds and decaying slowly over the next 15 seconds.
Keep the Mainstays?
How much does retinal mapping change traditional exam and referral protocol?
Dr. DeLoach says he uses the RTA as a tool for examining the posterior pole closely and then deciding whether to refer to a retinal specialist for fluorescein angiography and, possibly, laser treatment. If the patient presents with good visual function, clinical examination does not show extensive ischemic changes, and the RTA doesnt show significant edema, hell continue to monitor the patient and avoid invasive testing. If any of the clinical findings are rather extensive, or the RTA shows rather extensive edema, Im certainly more comfortable getting a retinal consult on those patients, he adds.
He emphasizes that tests such as the RTA do not obviate the need for fluorescein angiography, but decreases the need, limiting it it to the more appropriate cases. But it certainly doesnt eliminate that very valuable diagnostic tool. It just gives us a more non-invasive alternative in many cases, he says.
Zeiss Humphrey says that fluorescein angiography and its OCT unit are complementary, but after an initial angiogram, OCT can sometimes eliminate the need for subsequent invasive testing. Still, you might need to obtain an additional angiogram to assess the severity of vascular dropout around the fovea in patients with more severe cases of diabetic retinopathy.
Dr. Alexander says that these devices, while important, dont replace the mainstays of caring for diabetic patients. These include regular dilated fundus exams, communication with other practitioners caring for the patient, and paying close attention to the A1C glycosolated hemoglobin levels as an indicator of how well the patients condition is being controlled.
Relying solely on advanced technology is unsound. Says Dr. Alexander: Ive said this before and will continue to say it: The best diagnostic tool you have available is really between your ears.
Dr. DeLoachs diabetic patient whose vision may have been saved by his suspicions would probably agree.