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as described by Lewis et al. (59). In these cases, vitrectomy is beneficial. In other cases, the posterior hyaloid appears to be slightly reflective, detached from the retinal surface in the perifoveal area and attached at the foveal center. This aspect is quite common, and corresponds to early posterior vitreous detachment (57, 58).
Clinical Applications of OCT in Diabetic Macular Edema
Several reports have studied the incidence of individual OCT patterns in diabetic macular edema and their clinical significance in an attempt to predict response to treatment and visual outcomes. In a study of 164 eyes with diabetic macular edema, the most common OCT pattern of cystoid macular edema was diabetic macular edema, which was found alone in 39.5% of eyes and in combination with other patterns in 97% of eyes (54). Other authors reported an incidence of diffuse retinal thickening of 60–88% (7, 53, 60). Cystoid macular edema has been reported to be present in 15–55% of eyes with diabetic macular edema (7, 53, 54, 60). Cystoid macular edema in the absence of other patterns was found in 11.9% of cases (53). Kim et al. found posterior hyaloidal traction in 15.6% of eyes (54). Interestingly, the majority (81.4%) of eyes with posterior hyaloidal traction did not show evidence of a traction retinal detachment. However, it is possible that with longer follow-up, posterior hyaloidal traction may eventually lead to tractional retinal detachment. Serous or traction retinal detachments occur less frequently than the other three OCT patterns. Serous retinal detachment without posterior hyaloidal traction has been reported in 7–15% of eyes with diabetic macular edema (7, 53, 54). Tractional retinal detachment due to posterior hyaloidal traction has been reported in less than 4% of cases (7, 29, 54).
Although diffuse retinal thickening is often found as a single pattern of diabetic macular edema, the remaining OCT patterns usually do not appear alone. The most common combination described is diffuse retinal thickening with cystoid macular edema, seen in 29% of cases (54). Other common patterns include: diffuse retinal thickening, cystoid macular edema, and posterior hyaloidal traction (7.3%); diffuse retinal thickening, cystoid macular edema, and serous retinal detachment (6.9%) (Fig. 20); diffuse retinal thickening and posterior hyaloidal traction (5.8%) (Fig. 21); diffuse retinal thickening, cystoid macular edema, posterior hyaloidal traction, and tractional retinal detachment (0.7%); and diffuse retinal thickening, posterior hyaloidal traction, and tractional retinal detachment (0.4%). Retinal detachment alone, either serous or tractional, has not been described.
Fig. 20. OCT scan showing diffuse macular edema, cystoid macular edema, and subretinal fluid.
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Fig. 21. OCT scan showing diffuse retinal thickening and posterior hyaloidal traction. An intraretinal cystoid cavity is present as well.
Compared with normal foveal thickness values, which range from 150 to 200 m, mean retinal thickness in patients with diabetic macular edema has been reported between 400 and 500 m, and range as high as 1,000 m (7, 53, 54, 60). OCT has also been used to demonstrate daily variation in the severity macular edema (61). In addition, retinal thickness varies depending on the OCT pattern present. Although mean retinal thickness is elevated in each of the five diabetic macular edema patterns, patients with a retinal detachment, either serous or tractional, have the greatest retinal thickness (53, 54). Patients with cystoid macular edema, posterior hyaloidal traction without tractional retinal detachment, and diffuse retinal thickening have increased retinal thickness but not to the same degree as patients with retinal detachment. Patients with cystoid macular edema have a greater increase in retinal thickness compared with patients with diffuse retinal thickening alone.
Several studies have demonstrated that foveal thickness measured by OCT is correlated with visual acuity in patients with DR (7, 29, 33, 53–55, 62, 63). In particular, cystoid macular edema and posterior hyaloidal traction without tractional retinal detachment have been associated with worse visual acuity (54). Kim et al. found that OCT patterns containing cystoid macular edema had the most profound effect on visual acuity, especially at lower retinal thickness (54). Similarly, the presence of vitreomacular traction in the setting of diabetic macular edema has been associated with worse visual outcomes (29, 54). Conversely, the presence of serous retinal detachment was not correlated with poorer visual acuity. However, other studies have not shown this correlation. A likely explanation for this disparity is the fact that the OCT cannot visualize photoreceptor function, so patients with longstanding diabetic retinopathy may have poor vision due to retinal abnormalities not visible with the scanner.
In recent years, OCT has been used extensively in the evaluation of treatment response of diabetic macular edema. Progression of macular thickening and its response to treatment with laser photocoagulation (64, 65), subtenon’s or intravitreal injection of triamcinolone acetonide (66–68), or vitrectomy (56, 69, 70) have been monitored using serial OCT examinations. Retinal thickness measurement by OCT has been a main
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outcome studied by the Diabetic Retinopathy Clinical Research (DRCR) Network, a collaborative multicenter research effort that was formed in 2002. In one recent study, OCT was used to conclude that peribulbar injection of triamcinolone acetonide is unlikely to have any significant benefit in the treatment of diabetic macular edema in patients with good visual acuity (71). Clearly, the ability to monitor changes in retinal thickness by OCT as a response to treatment has become invaluable to the assessment of the effects of current and new treatments.
A number of studies compared the use of OCT with slit-lamp biomicroscopy and stereo fundus photography in the detection of macular thickening. OCT was found to be sensitive to small changes in retinal thickness despite normal findings by slit-lamp biomicroscopy (33, 38). Brown et al. reported good agreement between OCT and contact lens examination for the presence or absence of foveal edema when OCT thickness was considered normal (≤ 200 m) or significantly increased (> 300 m) (6). However, when OCT foveal thickness was mildly increased (201–300 m), slit-lamp biomicroscopy was sensitive in only 14% of cases.
Since guidelines for treatment of diabetic macular edema are based on stereoscopic diagnosis of “clinically significant” macular edema as defined by the ETDRS (2), the value of treatment of early, or “subclinical” retinal thickening detected by OCT is still unknown. Furthermore, the best criteria for detecting subtle changes in retinal thickness remain to be defined and validated. Similarly, OCT criteria for evaluating the progression of nonclinically significant diabetic macular edema have not yet been clearly defined.
Prior to the development of OCT, stereo fundus photography had been the accepted gold standard for the evaluation of diabetic macular edema. Although stereo fundus photography has high resolution over the whole photographic field, quantifying retinal thickness is difficult using this method as it is dependent on the stereopsis of the observer and the quality of the fundus photographs. Strom et al. found a significant degree of agreement between stereo fundus photographs and OCT for both foveal and central macular area (1,000 m in diameter) thickening (72). Exact agreement on location was found in 89.4% of cases. When comparing measurements of the area of retinal thickening, exact agreement was found in 84.1% of cases. However, stereo fundus photographs tended to be more sensitive than OCT for the detection of retinal thickening in peripheral ETDRS fields. Goebel et al. found a good correlation between stereo fundus photographs and OCT (r = 0.77), although OCT was able to detect 12.6% of eyes with macular edema that were missed by stereo fundus photographs (73).
OTHER RETINAL IMAGING MODALITIES IN DIABETIC
RETINOPATHY
The retinal thickness analyzer (RTA) uses a single vertical narrow green He–Ne (543.3 nm) laser slit beam that is projected at an angle on the retina while a camera records the backscattered light (74). Due to the oblique projection of the beam and the transparency of the retina, the backscattered light returns two peaks corresponding to the vitreoretinal and the chorioretinal interfaces. The calculated distance between the two light peaks determines the retinal thickness at a given point. During scanning, the
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RTA acquires a red-free fundus image. Using blood vessels as guidelines, the registration software automatically overlays the map on the fundus image, enhancing reproducibility and measurement accuracy.
A number of studies (75–77) have compared the OCT and RTA in the detection of retinal thickening. Both instruments can detect small increases in retinal thickness of 20–40 m and have been reported to yield reproducible measurements of foveal thickness (75). Pires et al. (76) found OCT to be less sensitive than the RTA in detecting localized increases in retinal thickness in the early stages of diabetic retinal disease. Goebel et al. showed that retinal thickness values by RTA are lower than those by OCT for the same patient population (73). Agreement of stereo fundus photography was consistently better with OCT than with RTA. The authors suggested that the algorithm in the RTA gets less accurate signal with greater retinal thickness because the video signal from the pigment epithelium is attenuated and blurred. The RTA may therefore be more appropriate in initial diabetic retinal disease rather than in more advanced stages with severe morphological alterations. Polito et al. reported a much lower rate of successful foveal thickness reading for the RTA (62%) than for OCT (98%) (77). Neubauer et al. indicated that a greater proportion of falsely high thickness values might be present in RTA measurements (75).
Scanning laser ophthalmoscopy (SLO) measures retinal topography and maps the retinal surface (78). In the SLO, a narrow 1mm beam of laser traverses the optical axis to a single 10 m point on the fundus. A fundus image is then generated by scanning the laser over the retina in a raster fashion and detecting the reflected light with an avalanche photodetector. This signal is synchronously decoded to form a digital image. The capacity to carry out confocal imaging is a significant advantage of the SLO. By moving a confocal aperture between two end points chosen by the operator a large number of tomographic slices of the retina can be acquired. From this data, depth information on retinal features can be derived (79). Tong et al. suggested that this technology may be potentially useful in screening for asymptomatic diabetic macular edema using a new scoring system (80). Studies comparing OCT and SLO have not been performed to date.
CONCLUSIONS
The detection of retinal abnormalities in diabetic patients is vital for preventing the associated complications and subsequent loss of vision. With the emergence of new treatments for the prevention of diabetes-induced damage to the retinal microvasculature, early discovery of diabetic retinopathy is of primary importance. Fluorescein angiography remains an indispensable procedure for the diagnosis of macular edema, retinal ischemia, and proliferative diabetic retinopathy. Optical coherence tomography has become the gold standard test in the early detection of macular edema, vitreomacular traction, and subretinal fluid that are not detectable by biomicroscopy or fluorescein angiography. Technological advances such as the ultrahigh-resolution OCT will certainly provide ophthalmologists with greater understanding of retinal pathology in diabetic retinopathy. These diagnostic modalities will likely change how and when patients are treated, and may lead to the development of more effective therapies and improved outcomes.