Fig. 8.1
Diffuse retinal thickening. SD-OCT showing sponge-like swelling, low reflective, expanded and irregular areas of the retina, and small amount of subfoveal fluid
Cystoid macular edema (Fig. 8.2)
Fig. 8.2
Cystoid macular edema. SD-OCT showing hypo-reflective fluid-filled cystic cavities within the outer retinal layers, separated by hyper-reflective septae of neuroretinal tissue
Serous retinal detachment (Fig. 8.3)
Fig. 8.3
Serous retinal detachment. SD-OCT showing fluid accumulation between the detached retinal pigment epithelium and neurosensory retina
Posterior hyaloidal traction (Fig. 8.4)
Fig. 8.4
Posterior hyaloidal traction. SD-OCT showing attached posterior hyaloid inducing some tractional effect possibly exacerbating the underlying edema. The hyper-reflective foci with posterior shadowing represent small exudates
Posterior hyaloidal traction with tractional retinal detachment (Fig. 8.5)
Fig. 8.5
Posterior hyaloidal traction (more severe form)
Of these, the most common pattern is diffuse retinal thickening (39.5 %), and the least common are posterior hyaloidal traction (12.7 %) and tractional retinal detachment (2.9 %) (Ahmadpour-Baghdadabad et al. 2013; Kim et al. 2006; Otani et al. 1999). The other patterns typically do not appear in isolation, with the most common combination being diffuse retinal thickening and CME (29.0 %). Serous retinal detachment is more common in males and patients with a serum triglyceride ≥200 mg/dL (Ahmadpour-Baghdadabad et al. 2013). Patterns that are significantly associated with a decrease in visual acuity are diffuse retinal thickening, CME, and posterior hyaloidal traction. Some studies have suggested that the greatest decrease in vision occurs in the presence of CME and posterior hyaloidal traction, but others indicate that the degree of visual loss may not necessarily correlate with the type of pattern seen (Ahmadpour-Baghdadabad et al. 2013; Shimura et al. 2011). While the relationship between retinal thickening and decreased visual acuity is a characteristic of DME, it is not observed in macular edema secondary to other diseases, including CRVO, Irvine-Gass syndrome, posterior uveitis, and retinitis pigmentosa (Catier et al. 2005).
Soliman et al. investigated the morphological patterns of DME and identified what they believed to be progressive stages. In their scheme, stage 1 consists of leakage on FA without any changes visible via OCT. Stage 2 consists of thickening of the outer nuclear layer (ONL) and/or Henle’s layer. Stage 3 includes the morphological changes of stage 2 plus cystic changes of the ONL and/or Henle’s layer. Stage 4 is similar to stage 3 but also includes cystic changes of the inner nuclear layer (INL). Stage 5 has the appearance of stage 4 plus serous retinal detachment. Solimon correlated increasing central macular thickness as well as decreased BCVA with each successive stage (Soliman et al. 2007).
Kim et al. investigated the response to focal laser photocoagulation in eyes with DME and diffuse retinal thickening, CME, and/or vitreomacular interface abnormalities and found that all patterns showed a significant decrease in thickening after treatment. Eyes with DME had a greater reduction in thickening and improvement in visual acuity after treatment than eyes with either CME or vitreomacular interface disease, and persistent edema after laser treatment was more common in the CME and vitreoretinal interface anomaly groups (Kim et al. 2009).
While the ETDRS established focal laser photocoagulation as the gold standard of treatment for CSDME more than 30 years ago, clinicians have been increasingly exploring the use of anti-VEGF agents for the treatment of DME. Shimura et al. followed 143 eyes with DME without any history of prior treatment for 12 weeks after a single intravitreal injection of 1.25 mg of bevacizumab. Eyes with vitreomacular interface abnormalities were excluded from the study, but eyes with diffuse macular thickening, CME, as well as serous retinal detachment all experienced a decrease in foveal thickness after injection. The percentage of improvement was significantly greater in the CME and diffuse retinal thickening eyes than in the eyes with serous retinal detachment. Similarly, the visual acuity improved in all patterns after injection, but the effect was significantly more pronounced in the CME and diffuse retinal thickening eyes than in the eyes with serous retinal detachment. The foveal thickness decreased gradually after injection and reached its nadir at approximately 8 weeks in all groups, after which thickening began to recur. The magnitude of improvement in foveal thickening was inversely proportional to the duration of diabetes in CME and diffuse retinal thickening groups, but not in the serous retinal detachment group. Additionally, for unclear reasons, the CME eyes appeared to cluster into two groups: a high-sensitivity group with a greater than 40 % maximal reduction in foveal thickness and a low-sensitivity group with a less than 30 % maximal reduction (Shimura et al. 2013).
Cheema et al. found a positive treatment effect in terms of improved BCVA at 6-month follow-up after a mean of 2.05 intravitreal injections of bevacizumab in patients with focal cystoid edema, which they defined as limited retinal thickening with cyst formation and preservation of the macular contours; they found no significant improvement in BCVA in eyes with diffuse DME, typical CME, or SRF despite significant decreases in central macular thickness. Eyes with vitreomacular interface abnormalities were excluded from analysis (Cheema et al. 2014).
While the above studies suggest that different patterns of DME as determined by OCT may respond differently to intravitreal bevacizumab, conflicting data exists. A retrospective study by Koytak et al. found no variation in improvement in BCVA after a single injection of bevacizumab between eyes with diffuse retinal thickening, CME, or serous retinal detachment. However, in this study, eyes were classified by the predominant OCT pattern of macular edema (Koytak et al. 2013). Regardless, some variability may exist in the way different authors sort OCT images into different patterns of macular edema. A well-designed clinical trial might help to clarify the responses of different OCT patterns of macular edema to anti-VEGF therapy and improve our understanding of appropriate dosing intervals.
Intravitreal corticosteroids have also been used in the treatment of DME. Shimura et al. investigated whether the effectiveness of intravitreal triamcinolone acetonide depended on the pattern of DME as determined by OCT. They found that while there was no difference in baseline visual acuity between the groups, and all groups experienced an improvement in BCVA after treatment with triamcinolone, the improvement was much better in eyes with diffuse retinal thickening and CME as compared to eyes with serous retinal detachment. Intravitreal triamcinolone had no significant effect in eliminating subretinal fluid in this study (Shimura et al. 2011).
8.3 Macular Thickening
The average retinal thickness in an area 500 μ in diameter centered on the fovea is 174 ± 18 μ, in healthy individuals and almost never exceeds 216 μ. Central foveal thickness in healthy patients is, on average, 152 ± 21 μ. In contrast, a central foveal thickness of 200–250 μ or more is considered by many authors to signify the presence of edema (Kim et al. 2009). Figure 8.6 demonstrates diffuse retinal thickening with loss of the foveal contour and epiretinal membrane formation. Sánchez-Tocino et al. found a maximal foveal thickness of 180 μ in normal subjects. They calculated a sensitivity of 93 % and specificity of 75 % for detecting CSDME when using this number as threshold for measurements made via the manual caliper tool on Zeiss OCT machine, as compared to the gold standard ETDRS methods (Sánchez-Tocino et al. 2002).
Fig. 8.6
Diffuse retinal thickening with epiretinal retinal membrane. SD-OCT showing complete loss of the foveal contour with hyper-reflective signal seen just anterior to the neurosensory retina
As subtle or focal macular thickening can be challenging to see with slit-lamp ophthalmoscopy; the assessment of macular thickness by OCT can be an effective screening tool for the detection of DME. Goebel and Kretzchmar-Gross compared foveal macular thickness as measured by OCT vs standard ETDRS methods for the diagnosis of CSDME and determined that OCT has a sensitivity of 89 % and specificity of 96 % (Goebel and Kretzchmar-Gross 2002). Most commercial OCT devices produce a macular thickness map with measurements at the central fixation point (Panozzo et al. 2002) and ETDRS-like macular areas, making correlation with clinical observations according to the ETDRS protocol straightforward. Figure 8.7 is an example report from a Stratus OCT device. Macular thickening correlates with a decrease in visual acuity in eyes with diffuse retinal thickening and CME, but not in eyes with subretinal fluid (Shimura et al. 2011).
Fig. 8.7
Stratus OCT report. This OCT device produces a macular thickness map and reports the average thickness in each of nine ETDRS-like regions of the macula. Average thickness measurements at various points, including the fovea, are tabulated and compared to an age-matched normative database. Macular volume is also quantified
8.4 Limitations
Measurements of retinal thickening will differ between OCT machines of different manufacture due to dissimilarities in their algorithms for segmentation. In particular, while all devices identify the vitreomacular interface as the inner retinal border, they may differ on the signal used to delimit the outer retinal boundary. For example, the older versions of the RTVue software treat the IS/OS junction as the outer retinal border, while newer updates of the RTVue software, the Cirrus HD-OCT and the Spectralis, use a band corresponding to the RPE/Bruch’s membrane/choriocapillaris complex (Hee et al. 1995). One practical implication of this is that sequential measurements of macular thickness in the same eye made with different OCT implementations are not directly comparable. Also, different OCT devices will have different, proprietary normative databases for age, sex, and race (Sikorski et al. 2013).
An additional consideration is that signal strength, artifacts, and other imaging defects may introduce errors in image segmentation that impact the measurement of macular thickness. These types of errors include failure to identify the inner or outer retinal boundaries, truncation of the image due to inappropriate depth, and incorrect localization of the foveal center. The clinician must be cognizant of these factors when interpreting OCT measurements and assessing imaging quality. Manual correction of many of these types of errors is possible on most commercial OCT platforms. The savvy clinician may use false color images to examine subtle retinal structures, but should be aware that false color may also introduce image artifacts (Sikorski et al. 2013).
OCT of the macula in DME best serves the retinal physician as an adjective study besides careful clinical observation, fundus photography, and FA. A Cochrane review designed to evaluate the diagnostic accuracy of OCT for detecting CSDME concluded that OCT is not sufficiently accurate to diagnose the central type of macular edema (Wolf-Schnurrbusch et al. 2009).
8.5 Cystoid Macular Edema
Persistent macular edema leads to the formation of cystoid spaces consisting of septate pockets of fluid, primarily in the Henle’s layer and the outer plexiform layer, but can sometimes also be found in the inner plexiform layer. Perifoveal cysts tend to localize mainly to the outer retinal layers (Otani et al. 1999). They appear on OCT as areas of hypo-reflectivity. Figure 8.8 shows typical CME with larger cysts in the outer retinal layers and the beginnings of small cyst formation in the inner layers.
Fig. 8.8
Cystoid macular edema. SD-OCT showing large perifoveal cysts in the outer retinal layers. Small cysts are seen in the inner rental layers
Ex vivo histological specimens of a small number of patients with DME and early OCT-based studies lead to the hypothesis that cystoid macular edema results from long-standing cytoplasmic swelling of the Muller cells, leading to their necrosis and the formation of the cystic cavities (Fine and Brucker 1981; Yanoff et al. 1984). More recent high-definition OCT studies suggest that the fluid collection may in fact be extracellular. Regardless, cellular dysfunction and eventual death does result.
In long-standing macular edema, the cystic cavities may coalesce into one large foveal cavity (Fig. 8.9). Secondarily, these changes may produce OCT findings consisting of obscuration of the normal laminar structure, flattening of the foveal depression, and retinal thickening. Cysts may enlarge in size to span the full thickness of the retina which may lead to atrophy and profound loss of vision. Figure 8.10 shows such an eye with severe CME and disruption of the outer segments. Fluid can be seen underneath the neurosensory retina in some cases (Koleva-Georgieva and Sivkova 2009). Cystoid changes are less common in macular edema secondary to ERM alone than it is in DME (Otani et al. 2010).
Fig. 8.9
Cystoid macular edema. SD-OCT showing small cysts that have coalesced to form one large cyst
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