The diagnosis and management of diabetic macular edema depend on the traditional techniques of slit-lamp examination and fluorescein angiography. Although fluorescein angiography is sensitive to vascular leakage, which causes macular edema, actual retinal thickening is better correlated with loss of visual acuity.1
Thus, the ETDRS guidelines for clinically significant macular edema are based on slit-lamp observation of macular thickening or hard exudate associated with macular thickening within 5.00 μ
m of the central fovea, independent of the angiographic findings. We previously have shown that OCT is an effective technique for monitoring central foveal thickness in patients with macular edema. 7
Single measurements of retinal thickness in the central fovea, however, provide an incomplete clinical picture because extrafoveal macular edema is neglected. In this study, a radial spoke pattern of six optical coherence tomograms was used to obtain geographic measurements of macular thickness. Macular thickness was displayed quantitatively, averaged over nine ETDRS-type regions, and as a false-color topographic map. Although many methods
ould have been used to sample retinal thickness throughout the macula, the radial scanning pattern concentrated measurements in the central macula where information was most important. Additionally, the individual OCT images permitted visualization of intraretinal features such as cysts and hard exudate (e.g., Figs , ), which would not have been available from other scanning patterns that did not have the A-scans spaced closely in one dimension.
The radial pattern of six tomograms sampled macular thickness at all clock-hours. Bilinear interpolation in polar coordinates was used to estimate thickness in the wedges between each tomogram for the false-color display. No interpolation was used to compute average thickness by ETDRS region. This protocol would be expected to miss very focal edema situated in a wedge that spanned less than a clock-hour. In our experience, the likelihood of this occurring was minimal, especially near the fovea where the tomograms were spaced more closely. With six OCT images used to radially map macular thickness, the arc length of a clock-hour 500 μm from the center was approximately 250 μm. More detailed mapping could be obtained, if desired, by increasing the number of tomograms in the radial pattern. Because each image was acquired in 2.5 seconds, the total time required to perform all six scans in a given eye usually was less than a minute. The radial scanning pattern kept the patient's fixation constant for all tomograms, which enabled the six scans to be performed in succession after the initial alignment.
The topographic mapping protocol was useful in longitudinally monitoring patients for the development of macular edema and for following the resolution of edema after laser treatment (e.g., cases 2–4). Geographic information was helpful because edema often presented or began to resolve outside of the fovea before affecting central macular thickness (e.g., case 3). The false-color map of retinal thickness provided an intuitive and efficient method of comparing retinal thickness over several visits, which could be directly compared with slit-lamp observation.
The OCT topographic map of retinal thickness generally correlated with conventional clinical examination. Retinal thickening or hard exudate observed on slit-lamp biomicroscopic analysis almost always correlated with increased thickness on OCT, but there were some occasions in which OCT detected thickening in the absence of any abnormality on slit-lamp examination. Both measurements of central macular thickness and measurements of foveal thickness averaged over a central disk of 500-μ
m radius appeared to be more sensitive than slit-lamp examination for evaluating clinically significant macular edema. Edema was difficult to detect clinically when there was no hard exudate in the central macula and diffuse rather than focal macular thickening was present, reducing the variation in retinal surface contour. Optical coherence tomography retinal thickness also generally correlated with regions of fluorescein leakage; however, increased macular thickness occasionally was evident on OCT in the absence of leakage. Both single measurements of central foveal thickness and measurements averaged over the 500-μ
m central disc essentially were equivalent in detecting clinically significant thickening. Optical coherence tomographic measurements of macular thickness averaged over eyes with the same visual acuity correlated with visual acuity in diabetic patients both with and without retinopathy. The correlation between central thickness and visual acuity (r2
= 0.79) corroborated previous studies.7
Optical coherence tomography appears to be a promising method for screening for the early development of diabetic macular edema. Optical coherence tomography is without contact and noninvasive, and the apparent brightness of the predominantly infrared light is significantly less than the visible illumination from conventional indirect ophthalmoscopy. Macular edema can be detected by comparing thickness measurements with values from a normal population, with earlier baseline measurements from the same patient, or with measurements from the contralateral eye. In our series, the normal variation (SD) in average retinal thickness was small (15 μm outside the fovea and approximately 20 μm centrally). Macular thickness was not correlated with age, but was slightly larger in males compared to females. The effect of axial eye length on foveal thickness was not investigated. Left and fight eyes also were highly correlated among healthy subjects. Among normal subjects, the mean ± SD absolute difference in left and fight foveal thickness was 6 ± 9 μm. In contrast, absolute foveal thickness varied over a range (±SD) of 36 μm. The difference between the intrapatient and interpatient variation was evidence of the high precision of the OCT measurements and suggested that the comparatively larger interpatient variability was because of differences in actual thickness rather than measurement errors. Both the small variation in thickness among normal eyes and the high correlation between right and left eyes suggested that OCT was highly sensitive to small increases in macular thickness that would characterize early macular edema.
These results indicate that OCT has potential to screen patients with early nonproliferative retinopathy for the development of macular thickening. We also attempted to investigate whether some patients with diabetes might have early macular edema develop before the onset of ophthalmoscopically visible retinopathy. Abnormal macular thickening was suspected if either the absolute macular thickness was greater than the maximum observed for normal eyes (i.e., >216 μm) or if the difference in foveal thickness between the right and left eyes was greater than two SDs larger than the mean difference for normal eyes (i.e., >24 μm). (Alternatively, a two-SD figure of 210 μm could have been used to screen absolute macular thickness.) Three patients with diabetes () and one normal subject showed a suspicious difference in foveal thickness between right and left eyes based on these criteria. Two of the patients with diabetes (A, B) also had abnormally thick foveae in one eye according to these criteria. One of these two suspicious patients (A) had an unacceptable reproducibility figure of 53 μm, indicating a low reliability for that measurement. Patient B, however, exhibited acceptable reproducibility and a left foveal thickness, which was both greater than all normal eyes and increased significantly compared to the patient's contralateral eye. Although patient B had a visual acuity of 20/20 in this eye, based on these findings, we believe that patient B would be a candidate for more frequent and detailed follow-up in his left eye, perhaps including fluorescein angiography.
Because all OCT images in the radial pattern intersected in the center, the SD of the six central thickness measurements provided an estimate of the test reproducibility and reliability. This reproducibility figure typically varied between 5 and 20 μm for normal subjects. Eyes with retinopathy tended to exhibit poorer reproducibility. Larger deviations suggested imperfect fixation and could be used to quantify the reliability of the OCT images. In patients with eccentric or varying fixation, the central fovea often was displaced laterally slightly from the center of the OCT image. In these cases, the computer provided an estimate of the lateral displacement by identifying the position of minimum total intraretinal reflectivity, which usually was characteristic of the relative absence of plexiform layers in central fovea. The examiner then was given a choice to offset the center of the OCT to this position. Human intervention was necessary because the computer occasionally would confuse the reduced intraretinal reflectivity, characterizing a cyst for the reduced reflectivity within fovea. We found that the examiner was able to identify the fovea based on its characteristic cross-sectional morphology in most eyes without severe edema. Thus, whereas complete manual identification of the fovea would have been feasible, the computer algorithm permitted a binary decision that minimized examiner bias. Future developments in the feature recognition algorithm should lead to a completely automated identification technique. In any case, imperfect fixation was a concern mostly for patients with advanced disease (e.g., case 2) and generally was not a factor in patients with more mild edema (e.g., cases 1, 3–5). Furthermore, the reproducibility figure provided an objective context within which one could interpret the OCT results from the patients with more problematic fixation.
Other potential sources of artifacts included refractive error and saccadic eye motion. The length of each OCT on the retina was computed from the angular deviation of the scanning mirrors by assuming a constant axial length for each eye. Differences in refractive power or magnification could therefore lead to inaccurate measurements of transverse dimensions that would affect the actual size of the nine ETDRS regions on the macula. This error could potentially be corrected in future studies with a simple multiplicative scaling factor derived from ultra-sonographic measurements of axial eye length or the glass refraction or both. 21
Measurements of central macular thickness were not affected by refractive error, and these measurements also could have been used to assess clinically significant macular thickening. Saccadic eye motions that occurred during the 2.5 seconds required for each of the six OCT images could result in inaccurate measurements of retinal thickness if there was significant local variation in thickness. Transverse eye motion was more problematic in patients with advanced disease and poor fixation. However, the influence of eye motion could be assessed in the central fovea with the reproducibility figure in a manner similar to fixation losses. A commercial OCT system is available with a scanning time of less than 1 second, which should reduce the impact of eye motion.
In summary, we found that OCT was a useful technique for quantitative measurement of retinal thickness in patients with diabetic macular edema. The topographic mapping protocol provided geographic information on macular thickness that was intuitive and objective. Future improvements in scanning time will allow more OCT images to be compiled into a more detailed and sensitive topographic map. This pilot study suggests that this method may become an effective diagnostic tool for screening patients with diabetes for the early development of macular thickening. Further studies are warranted to investigate the possibility of detecting retinal thickening before ophthalmoscopically evident retinopathy and to evaluate the impact of OCT on treatment outcome.