Both UHR and standard-resolution OCT enable the real-time, noninvasive visualization of most major intraretinal layers and perform comparably in differentiating thicker intraretinal layers such as the retinal nerve fiber, inner plexiform layer, INL, OPL, and ONL. Both UHR and standard-resolution OCT images also had excellent correlation with each other and with well-known retinal morphology.2,20,21
Relative to standard-resolution OCT, the UHR-OCT has an improved ability to visualize smaller structures such as the ELM and the backreflection arising from the IS/OS. The IS/OS in the outer retina is highly backreflecting and can be seen very clearly in UHR-OCT images. The identification of this IS/OS layer in the UHR-OCT image helps to establish the presence of this highly reflective feature in the standard-resolution OCT images as the IS/OS junction. The ability to visualize the ELM and the IS/OS is an important indicator of photoreceptor integrity or impairment. The ability to visualize and track photoreceptor morphology associated with macular hole formation and repair may play a role in further understanding the process of macular hole formation and may be useful in predicting and assessing the potential outcome of macular hole surgery.
In the lamellar hole (patient 1, ), both standard-resolution and UHR-OCT images indicate that the intraretinal structures of the outer retina (ONL and photoreceptor segments) are not involved in the formation of a lamellar hole. The photoreceptor OS in the foveola is involved in a stage 1b macular hole (patient 2, ), and it has detached and started to lift away from the RPE. A large cystic space above this detachment caused by the posterior hyaloid traction is also observed in this case. The UHR-OCT image of the stage 1b macular hole () has the resolution to show that the fine structures of the Henle’s fibers in the OPL are still intact and remain connected to the different parts of the retina. The UHR-OCT in this case also visualized small thin features that may be Mueller cells spanning the separation between the OPL and ONL (, yellow asterisk). The angled orientation of these structures is highly suggestive of traction on the photoreceptor. Ultrahigh-resolution OCT is also better than StratusOCT in demonstrating the preservation of the photoreceptor OSs in the foveola region (). The preservation of the photoreceptor OS demonstrated by the UHR-OCT image possibly can explain why macular hole surgery often has a successful outcome. Surgery can reappose the intact photoreceptors back to their normal anatomical position against the RPE and facilitate the recovery of visual function.
In the stage 2 macular hole (patient 3, ), both OCT images indicate the eccentric nature of the hole that is not centered on the fovea. The posterior hyaloid seen in both OCT images suggests that the pathogenesis of this macular hole may be due to oblique, as opposed to tangential, traction of the hyaloid. After macular hole surgery, the OCT images indicate the return of the normal macular morphology, and the patient experienced a concomitant improvement in vision. In the region of the macular hole before surgery, there was an absence of signal from the highly backreflecting IS/OS that reappeared after macular hole surgery had returned the normal macular appearance. This can be observed in both standard-resolution and UHR-OCT images (). Both standard-resolution and UHR-OCT images also show that this usually highly backreflecting IS/OS seems to be less backreflecting than normal (cf. ), and there seems to be some discontinuity of the junction in the region of the macular hole repair (). This suggests that small residual photoreceptor impairments could still be present after the surgery.
In the stage 3 macular hole (patient 4, ), the UHR-OCT image demonstrates that the improved resolution can enhance the visualization of the small cystic structures and better localize them to the ONL and INL. In the region of the macular hole, the preservation of the photoreceptor OSs is evident in the UHR-OCT image by following the highly visible IS/OS from the parafoveal area to the foveola (). The photoreceptor OS is continuous from the parafoveal region, where it is attached to the RPE, to the foveola region, where it is lifted away from the RPE, but still connected to the rest of the sensory retina (). The StratusOCT image does not have the resolution to resolve the fine features of the photoreceptor OSs.
In the stage 4 macular hole (patient 5, ), both standard and UHR-OCT images show the presence of cyst-like spaces in the ONL and a pseudo-operculum above the full-thickness hole. The UHR-OCT imaging () indicates that the photoreceptor layer morphology appears to be intact in the region of macular hole pathology, confirming that the structure observed is not a true operculum. After macular hole surgery (), the photoreceptor OS layer is reapposed back to its normal anatomical position against the RPE, except for the presumed residual elevation of the central photoreceptors in the foveola region (). This abnormal elevation of the central photoreceptors is seen in both StratusOCT and UHR-OCT images, but only the UHR-OCT image has the resolution to distinguish the photoreceptor OSs that are still present in this region (). This suggests that the foveolar elevation is caused by the continual shedding of the OS debris that cannot be completely reabsorbed by the RPE due to the lack of correct apposition of the OSs with the RPE. The lower resolution of StratusOCT () does not indicate the presence of OS tissue in the foveola elevation, which can incorrectly suggest subretinal fluid under the foveola elevation.
In comparison to StratusOCT images, all the UHR-OCT images were qualitatively superior in identifying small retinal features such as the ELM and the IS/OS. The IS/OS signal was previously interpreted incorrectly as the melanin-containing RPE.5,15
In this study, this thin high-backscattering feature of the outer retina is identified as the IS/OS junction anterior to the RPE signal, which is represented by the second high-backscattering feature in the outer retina (). The pathology cases presented in this study also support this reinterpretation of OCT signals in the outer retina. In full-thickness macular hole cases, there was no involvement of the backscattering features representing the RPE layer in the OCT images, whereas the features representing the photoreceptor layers were affected.
In all cases of macular holes (–), there seems to be a diminishment in the signal of the highly backreflecting IS/OS in the region of the macular hole and photoreceptor detachment. This reduction in reflection can possibly be attributed to the altered orientation of the IS/OS that is caused by lifting of the photoreceptor tissue away from the RPE.24–26
The OCT reflection from this IS/OS seems to arise from the abrupt change in optical index of refraction at the boundary between the ISs and the highly organized structure of the OSs.16
The photoreceptor OS contains stacks of membranous discs that are rich in the visual pigment rhodopsin, and this highly organized structure has a higher index of refraction,27
which causes the interface between inner and outer photoreceptor segments to be highly backreflecting in OCT. This interpretation is consistent with the findings from animal imaging studies,21
and it is also supported by the reappearance of this highly backscattering junction in the UHR-OCT images after macular hole surgery (, ). The abrupt change in optical index of refraction from the photoreceptor ISs to the highly organized stacks of the photoreceptor OSs seems to depend on the orientation of the membranous discs. This is consistent with previous studies demonstrating that photoreceptors exhibit directional sensitive waveguiding properties.24,28,29
In their anatomical position apposed to the RPE, the membranous stacks lie perpendicular to the direction of the incoming OCT beam and seem to cause a highly backscattering signal at the IS/OS junction. However, if the photoreceptor OS is detached and lifted away from the RPE, as in the region of the macular hole, the membranous stacks no longer lie perpendicular to the direction of the incoming OCT beam, and the highly backreflecting signal at the IS/OS seems to be absent (–). The UHR-OCT images reveal the preservation of the photoreceptor OSs in this region (, , , ), and the disappearance of the highly backscattering IS/OS in the region of the macular hole does not imply that the photoreceptor segments are completely destroyed. After macular hole surgery, which returns the stacks in the OSs back to their anatomical position perpendicular to the direction of the incoming OCT beam, the highly backreflecting signal of the IS/OS also returns in both standard-resolution and UHR-OCT images (; ). This feature, therefore, is an important indicator of photoreceptor integrity or impairment.
The ability of UHR-OCT to visualize fine features such as the ELM and the details of photoreceptor OS morphology indicates that the morphology of the photoreceptors is often preserved in the region of the macular hole where the sensory retina is detached from the RPE. This contrasts with standard-resolution OCT images, which can be incorrectly interpreted to suggest that sensory retinal tissue and photoreceptors are lost in the focal area of the macular hole. This finding was not reported in previous studies of macular holes with ophthalmoscopic examination or standard-resolution OCT.2,10–13
From the viewpoint of imaging with standard-resolution OCT, special attention should be paid to visualization of the highly backreflecting IS/OS, because this can be used as an indicator of photoreceptor integrity or impairment. Integrity of the photoreceptor OS would be a necessary though not sufficient condition for restoration of visual function. The ability to visualize and track photoreceptor morphology associated with macular hole formation may play a role in further understanding the process of macular hole formation. Ultrahigh-resolution OCT imaging may also be useful in predicting and assessing the potential outcome of macular hole surgery based on the morphologic appearance of the photoreceptor layers in the region of the macular hole. In our study, UHR-OCT imaging after macular hole surgery also demonstrated the ability to assess the outcome of surgical intervention to differentiate cases in which there is complete repair from those of residual disruption of the photoreceptor segments. In this study, UHR-OCT imaging was not used to alter the surgical treatment decision in any of the patients. A larger study of UHR-OCT imaging of preoperative and postoperative macular hole repair is needed before any efforts to use UHR-OCT to guide treatment planning are warranted.
In summary, we performed the first comparative imaging study between standard-resolution OCT and UHR-OCT of macular hole pathology and repair. Relative to standard-resolution OCT, UHR-OCT has an improved ability to detect smaller anatomical changes and better localization of these changes in the intraretinal layers. Ultrahigh-resolution OCT also allows, for the first time, detailed imaging of the photoreceptor morphology associated with the OS changes that occur with different stages of the macular hole. This ability of the UHR-OCT shows that, in many cases of macular hole formation, the photoreceptor OS is preserved, and early surgical intervention in these cases may have a positive outcome. Relative to standard-resolution OCT, UHR-OCT provides important information that can help form the basis for improving the understanding of macular hole pathogenesis and repair. Ultrahigh-resolution OCT images can also provide a baseline for improving the interpretation of standard-resolution OCT images of macular holes, which are widely available in clinical practice. Identification of the IS/OS in the UHR-OCT image helps to establish that this highly reflective feature is also present in the standard-resolution OCT images, and this junction can be used to indicate photoreceptor integrity or impairment, even in the standard-resolution StratusOCT images. The results from this study point out the importance of visualizing the IS/OS using both standard-resolution OCT and UHR-OCT to assess macular hole morphology. Further investigations will be required to understand if the improved ability of UHR-OCT to differentiate photoreceptor morphology can be used to improve diagnosis, predict surgical outcome, and improve treatment decisions.