PD-OCT composite images highlight microvasculature (red color) in three-dimensions noninvasively, similar to phase-resolved motion detection methods used in phase-variance OCT.
26 By combining a PD-OCT image with an Fd-OCT structural image, retinal vascular changes and the associated retinal morphologic changes can be studied simultaneously; this technique was a valuable tool for this study. The relative depth of the retinal vascular changes and their proximity to and association with retinal morphologic changes noted with Fd-OCT also can be studied unlike the two-dimensional en face image of the retinal vascular flow obtained with FA. This new technique allows visualization of retinal microcapillaries in the human retina as small as 5 to 10 μm in diameter. A previous study using an analogous phase-variance OCT showed that the size of the foveal avascular zone measured using this type of technology was similar to that obtained using FA in normal eyes and eyes with diabetic retinopathy.
26
PD-OCT, the more current prototype of this technology, was used in this study to identify the progressive perifoveal retinal vascular changes associated with various stages of MacTel. Three-dimensional retinal vascular imaging in vivo with this condition has not been reported previously. The currently theorized pathogenesis of this condition is based on only limited available histologic data, OCT morphologic findings, and clinical findings.
2,3
In our study, PD-OCT provided new insights to the pathogenesis of MacTel in vivo. In early stages of this disease (i.e., stages 1 and 2), where minimal changes are noted on funduscopy, OCT, MPOD, and FA, detectable abnormality in the retinal vasculature can be seen on PD-OCT as the retinal vessels that normally perfuse the superficial layers are seen abnormally diving into the deeper OPL. In later stages of the disease, these abnormal vessels appear to dive even deeper into the ONL, which itself may become affected by progressive atrophy of the outer retina associated with this condition. PD-OCT detected the eventual formation of full thickness retinal vascular channels with possible retinal–retinal or even retinal–subretinal anastomoses, which was theorized to characterize stage 4 MacTel. We recognize that it is sometimes difficult to distinguish deeper retinal layers in two-dimensional photos owing to overlying shadow artifact; however, characterization can still be made by observing vasculature without overlying vessels, by looking for oblique vessels, and by scanning serial B-scan images to follow the course of overlying vascular channels. Eventually these advanced vascular changes may lead to disciform scarring and severe vision loss characteristic of stage 5 disease, perhaps after the development of subretinal neovascular membrane. Our study did not include any eyes with stage 5 disease but demonstrates that the progression of retinal vascular changes and the associated concurrent retinal morphologic changes can be studied concurrently and in unprecedented detail using PD-OCT.
The retinal vasculature changes associated with various stages of MacTel noted in our study appear similar to that proposed by Gass and Blodi,
2 except we did not detect significant proliferation of the capillaries into the subinternal limiting layer in the early stages of this condition as proposed. Early disease tends to involve proliferation into the OPL, with further penetration of these vessels into the ONL with more moderate disease. These vascular changes occur concurrently with disruption of the various affected retinal layers and development of small intraretinal cysts and hyperreflective deposits, which are readily seen on Fd-OCT imaging.
27 Although there is no histologic correlate for the microcystoid spaces and the hyperreflective deposits seen on Fd-OCT,
28 they tend to be near abnormal retinal vascular signals and may represent formerly dilated vessels that have involuted or Müller-cell degeneration.
8,31 Similar microcystic changes and patches of photoreceptor atrophy or disruption have been described using Fd-OCT in eyes with toxic maculopathy from tamoxifen in the absence of any retinal vasculature abnormality on FA,
11 suggesting that they may result from direct damage to retinal cells rather than from retinal vascular abnormality.
With more advanced disease, focal perifoveal diffuse blurring of the retinal layers with disruption of the ELM and photoreceptor IS/OS junction become more apparent on Fd-OCT. Concurrent with these full-thickness changes on Fd-OCT is full-thickness retinal vascular proliferation extending perhaps from the subinternal limiting space to the subretinal space as proposed by Gass and Blodi
2,3 (stage 4;
Fig. 5). These changes are somewhat analogous to changes theorized with retinal angiomatous proliferation (RAP) lesions, a form of neovascular age-related macular degeneration.
3,29,30 The major difference between the two is that retinal–choroidal anastomoses with progression to choroidal neovascularization is not commonly seen in MacTel patients as it is in patients with RAP, although disciform scarring can occur with both conditions. In addition, drugs that inhibit VEGF appear to have minimal short-term effect in eyes with MacTel unlike eyes with RAP.
31,32
One major limitation of our study using this technology is that we have no histologic confirmation of our PD-OCT findings. Artificial flow signals can occur in both normal and MacTel eyes from shadow artifact and “non-zero phase differences.” These artifacts can be differentiated from true vascular signals in our study by following the vascular signal through serial B-scans and relying upon oblique retinal vessel orientation, which have no superficial artifact signal (see
Fig. 3D).