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To compare ultrahigh-resolution optical coherence tomography (UHR-OCT) technology to a standard-resolution OCT instrument for the imaging of macular hole pathology and repair; to identify situations where UHR-OCT provides additional information on disease morphology, pathogenesis, and management; and to use UHR-OCT as a baseline for improving the interpretation of the standard-resolution images.
Observational and interventional case series.
Twenty-nine eyes of 24 patients clinically diagnosed with macular hole in at least one eye.
A UHR-OCT system has been developed and employed in a tertiary-care ophthalmology clinic. Using a femtosecond laser as the low-coherence light source, this new UHR-OCT system can achieve an unprecedented 3-μm axial resolution for retinal OCT imaging. Comparative imaging was performed with UHR-OCT and standard 10-μm resolution OCT in 29 eyes of 24 patients with various stages of macular holes. Imaging was also performed on a subset of the population before and after macular hole surgery.
Ultrahigh- and standard-resolution cross-sectional OCT images of macular hole pathologies.
Both UHR-OCT and standard-resolution OCT exhibited comparable performance in differentiating various stages of macular holes. The UHR-OCT provided improved imaging of finer intraretinal structures, such as the external limiting membrane and photoreceptor inner segment (IS) and outer segment (OS), and identification of the anatomy of successful surgical repair. The improved resolution of UHR-OCT enabled imaging of previously unidentified changes in photoreceptor morphology associated with macular hole pathology and postoperative repair. Visualization of the junction between the photoreceptor IS and OS was found to be an important indicator of photoreceptor integrity for both standard-resolution and UHR-OCT images.
Ultrahigh-resolution optical coherence tomography improves the visualization of the macular hole architectural morphology. The increased resolution of UHR-OCT enables the visualization of photoreceptor morphology associated with macular holes. This promises to lead to a better understanding of the pathogenesis of macular holes, the causes of visual loss secondary to macular holes, the timing of surgical repair, and the evaluation of postsurgical outcome. Ultrahigh-resolution optical coherence tomography imaging of macular holes that correspond to known alterations in retinal morphology can be used to interpret retinal morphology in UHR-OCT images. Comparisons of UHR-OCT images with standard-resolution OCT images can establish a baseline for the better interpretation of clinical standard-resolution OCT images. The ability to visualize photoreceptors and their integrity or impairment is an indicator of macular hole progression and surgical outcome.
The initial classification, staging, and pathogenesis of idiopathic macular holes were based largely on clinical examination and fluorescein angiography.1,2 More recently, optical coherence tomography (OCT) has been employed. Optical coherence tomography provides noncontact, cross-sectional imaging of the retina at an axial resolution of 10 to 15 μm.3–9 It enables the direct, real-time, cross-sectional imaging of retinal pathology that could not previously be visualized in vivo. Optical coherence tomography imaging has improved the understanding of the pathogenesis of macular hole formation and yielded an improved staging of macular holes.10–13
Our group recently developed a new generation of ultra-high-resolution OCT (UHR-OCT) technology that significantly improves the axial image resolution.14,15 Using a state-of-the-art femtosecond laser as the light source for OCT imaging, this new technology achieves axial image resolutions of ~3 μm in the human eye. The enhanced imaging capabilities of UHR-OCT improve the visualization of intraretinal architectural morphology such as the ganglion cell layer (GCL), photoreceptor layers, and retinal pigment epithelium (RPE).16 Many of these structures undergo physical changes secondary to macular hole formation, and therefore, UHR-OCT can be a powerful tool for elucidating the process of macular hole formation and assessing the outcome of macular hole surgery.
This study compares imaging of macular hole pathologies using the new UHR-OCT system with that using the standard, 10-μm resolution, commercially available StratusOCT instrument (Carl Zeiss Meditec, Inc., Dublin, CA). The StratusOCT was introduced in 2002 and achieved a 4-fold increase in imaging speed or transverse pixel density relative to earlier commercial instruments. The StratusOCT provides more detailed cross-sectional information on retinal pathology than previous commercially available ophthalmic diagnostic techniques. To evaluate the morphology of macular hole and the outcome of surgical repair, comparative imaging with both UHR-OCT and StratusOCT was performed on a series of eyes with different macular hole pathologies. The objectives of the study were to identify situations where UHR-OCT provides additional information on disease morphology, pathogenesis, and management, and to use UHR-OCT as a baseline for better interpretation of standard-resolution OCT images. Imaging macular holes that produce known alterations of retinal morphology can be used to interpret features visible in UHR-OCT imaging, which then can be extended to standard-resolution OCT imaging. Conversely, the improved visualization provided by UHR-OCT enables a better understanding of macular hole pathology.
Optical coherence tomography imaging is analogous to ultrasound imaging, except that OCT performs imaging by measuring the echo time delay and magnitude of backreflected or backscattered light.10–13 A light beam is incident on the retina, and the echo time delay and magnitude of backreflected or backscattered light are measured to generate an axial scan similar to an A-scan in ultrasound. The light beam is scanned across the retina, and A-scans are measured at a series of different transverse positions. The resulting data are displayed as a false color or grayscale image, similar to a B-mode image in ultrasound. The OCT image represents a cross-sectional view of tissue, where the contrast in the image is produced by differences in backscattering or backreflection between different tissues.
Because echoes of light are too fast to be measured directly by electronics, in OCT measurements of light echoes are performed using a technique known as low-coherence interferometry. Light backscattered or backreflected from the eye (one arm of the interferometer) is correlated with light that has a known delay (from the second, reference arm of the interferometer). The axial resolution in OCT imaging is inversely proportional to the bandwidth of the light source used for imaging. Standard ophthalmic OCT instruments use superluminescent diode light sources that generate ~25 nm of bandwidth at an ~800-nm center wavelength, enabling an axial image resolution of ~10 μm.
A prototype, clinical UHR-OCT system suitable for performing studies in the ophthalmology clinic was developed. For this study, a specially designed, femtosecond, titanium:sapphire laser was used as the light source for OCT imaging.17 The titanium:sapphire laser generates ~125 nm of bandwidth, at an ~815-nm center wavelength, and enables an axial image resolution of ~3 μm in the eye. The prototype UHR-OCT ophthalmic instrument uses fiber optics, lenses, and other optical components that were specially designed to support the broad optical bandwidths required for UHR imaging. The use of lenses and optics with low chromatic aberration (variation of the focal lengths of lenses with wavelength) was important. Because of the broad bandwidth of the light source, special attention was required to cancel dispersion mismatch (resulting from variations in index of refraction with wavelength) in the 2 arms of the interferometer in the OCT instrument. Optical materials with identical dispersion characteristics were used in the 2 arms of the interferometer, and a 24-mm-long water cell was used in the reference arm to match the dispersion from the vitreous of the eye. The polarization of the 2 interferometer arms was also matched using fiber polarization controllers. This design was necessary to achieve ultrahigh axial image resolution. A high-speed, high-sensitivity, low–noise detection electronic system was built to achieve a high dynamic range and high-sensitivity UHR-OCT imaging. A computer was used to control the scanning pattern of the OCT beam on the retina, to acquire data, and to generate an OCT image on the display in real time. A more detailed description of the OCT instrument can be found in previous publications.14,15
The UHR-OCT prototype system was based on a slit-lamp biomicroscope that has an integrated charge-coupled device to provide a video image of the fundus. This provides a real-time view of the fundus during OCT imaging. The patient’s eye position was maintained using an internal fixation target, as in the standard StratusOCT instrument. To obtain high-quality fundus photographs for documentation, fundus photography was performed separately from OCT imaging. After OCT imaging was completed, both the UHR-OCT and the StratusOCT images were computer processed to correct for axial motion using standard reregistration algorithms. These motion correction algorithms have been used on all previous prototype and commercial OCT systems.3 A false color image display, similar to that used in the standard-resolution StratusOCT instrument, was chosen for the UHR-OCT images to better facilitate comparison of images from the different systems. False color images have the advantage that they can display a larger dynamic range than grayscale images because the observer can differentiate a wider range of colors than gray levels. However, it is important to note that color scales represent variations in backscattered or backreflected light and are not analogous to staining in histology.
Optical coherence tomography imaging is performed within well-established safe retinal exposure limits set by the American National Standards Institute.18 The American National Standards Institute standard for safe retinal exposure accounts for wavelength, duration, and multiple exposures of the same spot on the retina. The output of the femtosecond laser was coupled into a 100-m-long optic fiber before entering the OCT system to increase the pulse duration and reduce the peak intensities. Because the laser operates at a 50-MHz repetition rate, the output can be considered as a continuous wave rather than pulsed exposure. For the wavelengths and scanning conditions used in this study, the American National Standards Institute standards for maximum permissible ocular exposure are 1 mW (for 700-nm center wavelengths) and 1.54 mW (for 800-nm center wavelengths), assuming 30 consecutive scans in the same spot. For this study, UHR-OCT imaging was performed using up to 750 μW of incident optical power in the OCT scanning beam.
Imaging was performed using the standard-resolution, commercially available StratusOCT and our UHR-OCT prototype in the ophthalmology clinic of the New England Eye Center at Tufts University School of Medicine. The study was approved by the institutional review board committees of both Tufts–New England Medical Center and the Massachusetts Institute of Technology, and was compliant with the Health Insurance Portability and Accountability Act of 1996. Written informed consent was obtained from all of the subjects in this study before UHR-OCT imaging was performed. The diagnosis of macular hole was performed using standard dilated retinal examination and fundus photography. Comparative imaging was performed on 29 eyes of 24 patients with different stages of macular holes. Ultrahigh- and standard-resolution OCT images were obtained from each eye to make direct comparison of the macular hole images from the 2 instruments. In some eyes, macular hole surgery was performed subsequently, and comparative imaging was also performed after the surgery.
The StratusOCT image was generated using standard scans with a 2-mm axial depth and 6 mm in the transverse direction. The StratusOCT image had ~10-μm axial resolution and 20-μm transverse resolution in tissue and consisted of 1024 axial pixels and 512 transverse pixels (total, 524 288 pixels). The pixel spacing was 2 μm per pixel in the axial direction and 12 μm per pixel in the transverse direction. The UHR-OCT image was generated using scans with a 1.5-mm axial depth and 6 mm in the transverse direction. The UHR-OCT image had ~3-μm axial resolution and 15- to 20-μm transverse resolution in tissue and consisted of 3000 axial and 600 transverse pixels (total, 1 800 000 pixels). The pixel spacing was 0.5 μm per pixel in the axial direction and 10 μm per pixel in the transverse direction. The standard StratusOCT imaging protocol was followed on both systems to enable a direct comparison of the resulting images. Six radial macular scans 6 mm in length each were acquired, oriented at angles separated by 30° intervals, resulting in 3-mm rays at each clock hour emanating from the fovea.
Figure 1 shows standard and UHR-OCT images of the normal macula. The architectural morphology of the intraretinal layers in the OCT images correlates with well-known morphology of the retina in the macular region.19 In general, the nerve fiber layer and the plexiform layers are more optically backscattering than the nuclear layers and are seen as red, yellow, or bright-green false color in the OCT images.20–23 In both OCT images, the first highly backreflecting layer is the nerve fiber layer. The 3 low-backscattering intraretinal layers appear to be the GCL, inner nuclear layer (INL), and outer nuclear layer (ONL) and are seen as blue or black false color in the OCT images. The optically backscattering layers of the inner plexiform layer and outer plexiform layer (OPL) can be clearly visualized as bright green in both images. Ultrahigh-resolution OCT has the ability to identify fine retinal structures, such as the thin backreflecting external limiting membrane (ELM) just below the ONL, that are not visualized as clearly in standard-resolution OCT. The junction between the photoreceptor inner and outer segments (IS/OS) is visualized in both images as a thin highly backreflecting (red) feature in the outer retina, anterior to the RPE and choriocapillaris. This feature was incorrectly interpreted as being part of the RPE in previous publications.5,15 The melanin-containing RPE is also very strongly backscattering and is the second highly backscattering layer in the outer retina. The choriocapillaris and choroid layers are highly vascular and are visualized as optically backscattering layers. These vascular structures are highly scattering and limit the penetration of light and the imaging depth of OCT for distinct deeper choroidal structures. The interpretation of intraretinal features is also supported by imaging known alterations of retinal morphology associated with macular holes, as shown in the cases that follow.
A 58-year-old woman with 20/30 vision in her right eye was diagnosed with a lamellar hole upon clinical examination (Fig 2A). Figures 2B and C are cross-sectional StratusOCT and UHR-OCT scans taken across the lamellar hole. Comparing the standard-resolution StratusOCT image (Fig 2B) with the UHR-OCT image (Fig 2C) of the lamellar hole, it is evident that the lamellar hole in both images does not involve the structures of the outer retina (ONL, ELM, IS/OS), which remain intact and juxtaposed with the RPE. This finding helps to explain the relatively intact visual acuity (VA) of lamellar hole cases. Both StratusOCT and UHR-OCT images also show a separation between the ONL and the OPL in the region of the lamellar hole. In the standard-resolution image, most of the major intraretinal layers, such as the nerve fiber layer, inner plexiform layer, INL, OPL, ONL, IS/OS, and RPE, can be visualized, but the low-backscattering GCL and the thin backreflecting feature corresponding to the ELM are not well visualized in the standard-resolution image. The UHR-OCT image more clearly visualizes small features such as the ELM that are associated with photoreceptor segments in the outer retina. The IS/OS seems to be highly backreflecting and is visualized in both OCT images. This highly visible IS/OS may be used to detect the integrity of the photoreceptor OSs, even in standard-resolution OCT images.
A 64-year-old woman with 20/50 vision in her right eye was diagnosed with a stage 1b macular hole upon clinical examination (Fig 3A). Figures 3B and C are cross-sectional StratusOCT and UHR-OCT scans taken across the macular hole. Both OCT images show the posterior hyaloid attachment to the fovea. The images also show a small portion of the sensory retina that has detached from the RPE in the foveola region. Small cystic changes are also visible in the GCL and INL. The UHR-OCT image (Fig 3C) provides enhanced visualization of fine intraretinal features of the ELM and the Henle’s fibers of the OPL (Fig 3D, yellow asterisk). The UHR-OCT image provides an enhanced visualization of the very fine structures, which may be Mueller cells that span the separation between the ONL and the OPL. The angled orientation of these structures suggests traction on the photoreceptors.
In the region of central foveal elevation, both standard and UHR-OCT images show a reduced backreflection from the IS/OS in the region of the photoreceptor detachment. However, the increased resolution of the UHR-OCT image indicates that the photoreceptor IS and OS are still intact and attached to the ONL portion of the sensory retina, even in the region of the photoreceptor detachment (Fig 3D). Following the highly reflecting feature of the IS/OS from the parafoveal region into the region of the photoreceptor detachment, it is seen that the photoreceptor OS (Fig 3D) is still attached to the IS/OS. In response to the presence of the macular hole, the photoreceptor segments in this region seem to be detached from the RPE and lifted away from its anatomical position. There is a diminishment of the highly reflecting IS/OS in this region of detachment, and this may be attributed to the altered orientation of photoreceptor segments caused by the lifting away of photoreceptors from the RPE.24–26 These finer features involving the photoreceptor OS and IS/OS are difficult to differentiate in the standard-resolution image. Due to its lower resolution and difficulty in identifying the ELM and photoreceptor segments, the standard-resolution image may incorrectly suggest that there is a complete loss of outer retinal tissue in the region of the macular hole, when in fact the outer retinal morphology (EML and photoreceptor segments) is preserved, but only lifted away from the RPE in the foveola.
A 71-year-old woman with 20/200 vision in her right eye was diagnosed with a stage 2 macular hole upon clinical examination (Fig 4A). Figures 4B and C are the StratusOCT and UHR-OCT scans taken across the macular hole. Both standard-resolution and UHR-OCT images show the thin reflective posterior hyaloid that is connected to the lid of the stage 2 macular hole. The OCT images correspond to an eccentric macular hole where the opening of the hole is not centered on the fovea. Cystic spaces are present in the INLs of both OCT images (Fig 4B, C). In the region of the macular hole, the UHR-OCT image shows the preservation of the photoreceptor OS (Fig 4D) that is lifted away from the RPE. The lower resolution of the standard-resolution image does not clearly indicate the preservation of the photoreceptor OS in the foveola region.
After macular hole surgery, the patient’s vision improved to 20/40, and the macular hole appeared closed on funduscopic examination (Fig 4E). The StratusOCT and UHR-OCT scans (Fig 4F, G) show the restoration of the normal foveal depression and the resolution of the cystic intraretinal spaces. The photoreceptor IS and OS seem to be intact and connected to the RPE in the region where the stage 2 macular hole was before surgery. The UHR-OCT image shows a reappearance of the thin backreflecting ELM layer and the highly backreflecting IS/OS in the foveola region. Even though the StratusOCT image cannot distinguish the thin ELM layer in the outer retina, it can be used to demonstrate the return of the highly backreflecting IS/OS after the macular hole surgery. The presence of this feature suggests that the integrity of the photoreceptor OSs has been largely preserved, and there is minimal photoreceptor impairment. However, both standard-resolution and UHR-OCT images (Fig 4F, G) show that this usually highly backreflecting IS/OS seems to be less backreflecting after the macular hole surgery than in the normal adult eye (cf. Fig 1). There also seem to be small discontinuities of the IS/OS in the region of the repaired hole (Fig 4H), suggesting that small residual photoreceptor impairments may still be present. This may account for the lack of full VA recovery postoperatively.
A 64-year-old woman with 20/50 vision in her left eye had a chronic stage 3 macular hole (Fig 5A). The StratusOCT and UHR-OCT macular scans in Figures 5B and C clearly visualized a full-thickness macular hole. Cystic areas at the border of the macular hole seem to be localized in the ONL and INL of the parafoveal region. The UHR-OCT enhances visualization of the smaller cystic structures in the ONL. External to the macular hole, the neurosensory retinal layers seem to be normal in both the standard-resolution and UHR-OCT images. The improved resolution in the UHR-OCT image enables visualization and identification of the ELM, which is not clearly seen in the standard-resolution image. In the region of the macular hole, the UHR-OCT image again shows that the integrity of the photoreceptors is preserved, but they are detached from the RPE (Fig 5D). By following the highly visible backreflecting feature of the IS/OS from the parafoveal area to the region of the macular hole, the UHR-OCT image shows the photoreceptor OSs to be lifted away from the RPE, but still intact and connected to the rest of the sensory retina. The reduced backreflection from the IS/OS may be the result of misalignment of the photoreceptors from their normal anatomical position.24–26 The standard-resolution OCT image does not appreciably demonstrate the preservation of the photoreceptor OS.
A 64-year-old woman with 20/80 vision in her right eye was diagnosed with a stage 4 macular hole upon clinical examination (Fig 6A). The StratusOCT and UHR-OCT macular scans in Figures 6B and C demonstrate a full-thickness macular hole as well as cystic spaces in the ONL and OPL. A pseudo-operculum can clearly be seen above the region of the macular hole. At the boundary with the OPL, there are cystic changes in the ONL and INL. In the foveal region, the sensory retina has detached from the RPE, and the RPE is clearly visualized in the foveola. There is a slight shadowing of the RPE signal in the parafoveal region where there is edema of the sensory retina. The UHR-OCT image indicates that the architectural morphology of the ELM and IS/OS is preserved in the region of the macular hole (Fig 6D). The photoreceptor IS and OS are lifted away from their anatomical position against the RPE, but remain intact. Due to their lower resolution, it is difficult for standard-resolution images to differentiate the photoreceptor segment morphology in this detail.
After macular hole surgery, the patient’s vision improved to 20/40, and the macular hole appears closed (Fig 6E). The StratusOCT and UHR-OCT scans taken across the repaired hole (Fig 6F, G) demonstrate return of the normal foveal depression and the disappearance of cystic intraretinal spaces. Both images also show a small elevation of the outer retina away from the RPE in the central fovea, which may account for some of the residual postoperative visual impairment. Both standard and UHR-OCT images demonstrate the return of the highly backreflecting IS/OS in the parafoveal region, but the UHR-OCT image more clearly shows the reappearance of the thin backreflecting ELM layer. The ELM layer seems to be continuous after the surgery, but there is a residual elevation in the photoreceptor OSs in the foveola. The photoreceptor IS and OS seem to be intact and connected to the RPE in all regions, except for a small impairment in the foveola region (Fig 6H). This appearance of photoreceptor morphology is more difficult to evaluate in the standard-resolution image. In particular, the ELM is not visible, and the disruption of the photoreceptor OSs in the foveola cannot be differentiated from what appears to be subretinal fluid.
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, Fig 2), 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, Fig 3), 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 (Fig 3C) 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 (Fig 3D, 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 (Fig 3D). 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, Fig 4), 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 (Fig 4F, G). Both standard-resolution and UHR-OCT images also show that this usually highly backreflecting IS/OS seems to be less backreflecting than normal (cf. Fig 1), and there seems to be some discontinuity of the junction in the region of the macular hole repair (Fig 4H). This suggests that small residual photoreceptor impairments could still be present after the surgery.
In the stage 3 macular hole (patient 4, Fig 5), 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 (Fig 5C). 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 (Fig 5D). 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, Fig 6), 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 (Fig 6C) 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 (Fig 6F), 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 (Fig 6F, G). 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 (Fig 6H). 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 (Fig 6F) 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 (Fig 1B). 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 (Figs 3–6), 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 (Figs 4G, ,6G).6G). 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 (Figs 3–6). The UHR-OCT images reveal the preservation of the photoreceptor OSs in this region (Figs 3D, ,4D,4D, ,5D,5D, ,6D),6D), 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 (Figs 4F, G; 6F, G). 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.
The authors gratefully acknowledge the scientific contributions of A. Kowalevicz and I. Hartl and helpful scientific discussions with J. Enoch.
Presented in part at: Association for Research in Vision and Ophthalmology annual meeting, May, 2003; Fort Lauderdale, Florida.
Supported in part by the National Institutes of Health, Bethesda, Maryland (contract nos.: RO1-EY11289-16, R01-EY13178, P30-EY13078); National Science Foundation, Arlington, Virginia (contract no.: ECS-0119452); Air Force Office of Scientific Research, Arlington, Virginia (contract no.: F49620-98-1-0139); Medical Free Electron Laser Program, Arlington, Virginia (contract no.: F49620-01-1-0186); Austrian Science Foundation, Vienna, Austria (contract nos.: FWF P14218-PSY, FWF Y159-PAT, CRAF-1999-70549); a grant from the Massachusetts Lions Eye Research Fund, Inc., New Bedford, Massachusetts; and Research to Prevent Blindness, New York, New York.