Abstract
Objective
To describe the spectral-domain optical coherence tomography (SD-OCT) features of peripheral retinal findings using an ultra-widefield (UWF) steering technique to image the retinal periphery.
Design
Observational study.
Participants
68 patients (68 eyes) with 19 peripheral retinal features.
Main Outcome Measures
SD-OCT-based structural features.
Methods
Nineteen peripheral retinal features including: vortex vein, congenital hypertrophy of the retinal pigment epithelium (CHRPE), pars plana, ora serrata pearl, typical cystoid degeneration (TCD), cystic retinal tuft, meridional fold, lattice and cobblestone degeneration, retinal hole, retinal tear, rhegmatogenous retinal detachment (RRD), typical degenerative senile retinoschisis, peripheral laser coagulation scars, ora tooth, cryopexy scars (retinal tear and treated retinoblastoma scar), bone spicules, white without pressure, and peripheral drusen were identified by peripheral clinical examination. Near infrared (NIR) scanning laser ophthalmoscopy (SLO) images and SD-OCT of these entities were registered to UWF color photographs.
Results
SD-OCT resolved structural features of all peripheral findings. Dilated hyporeflective tubular structures within the choroid were observed in the vortex vein. Loss of retinal lamination, neural retinal attenuation, RPE loss or hypertrophy were seen in several entities including CHRPE, ora serrata pearl, TCD, cystic retinal tuft, meridional fold, lattice and cobblestone degenerations. Hyporeflective intraretinal spaces, indicating cystoid or schitic fluid, were seen in ora serrata pearl, ora tooth, TCD, cystic retinal tuft, meridional fold, retinal hole, and typical degenerative senile retinoschisis. The vitreoretinal interface, which often consisted of lamellae-like structures of the condensed cortical vitreous near or adherent to the neural retina, appeared clearly in most peripheral findings, confirming its association with many low-risk and vision-threatening pathologies such as lattice degeneration, meridional folds, retinal breaks, and RRDs.
Conclusions
UWF steering technique-based SD-OCT imaging of the retinal periphery is feasible with current commercially available devices, and provides detailed anatomical information of the peripheral retina, including benign and pathological entities, not previously imaged. This imaging technique may deepen our structural understanding of these entities, their potentially associated macular and systemic pathologies, and may influence decision-making in clinical practice, particularly in areas with teleretinal capabilities but poor access to retinal specialists.
Introduction
Since its introduction by Huang et al. in 1991, optical coherence tomography (OCT) imaging has revolutionized the understanding of the anatomical basis of normal, benign, and pathological macular features.1 Combining a non-invasive and facile ease-of-use with high-resolution structural imaging, OCT has been rapidly integrated into investigative clinical trials and routine practice as a readout of disease course and treatment, and also to guide clinical decision making.2, 3
Despite the centrality of OCT imaging in the diagnosis and treatment of macular diseases, this modality has been infrequently employed in the imaging of the peripheral retina, the site of many vision-threatening pathologies, including retinal tears, holes, detachments, and diagnostic mimics, such as peripheral retinoschsis.4 Routine imaging of peripheral retinal pathologies may enhance clinical decision-making, such as differentiating between subretinal and intraretinal fluid present in peripheral rhegmatogenous retinal detachments and retinoschisis, respectively.5, 6 The ability to image suspicious peripheral lesions via OCT may also catalyze telemedicine strategies to better diagnose and manage these entities in the after-hours, remote or resource-poor settings where retinal specialists may not be as readily available.7
Despite the unmet needs related to the dearth of OCT-based, high-resolution, cross-sectional image acquisition of peripheral retinal entities, few have been able to successfully achieve high quality SD-OCT imaging of the far retinal periphery. The term ‘widefield’ (WF) has been used by several authors to describe SD-OCT imaging of the retina within a 50o field of view, while ultra-widefield (UWF) has been reserved for the description of capturing 200o field of view in a single image.8-11 While en-face UWF-based fundus autofluorescence and fluorescein angiography imaging have illuminated our understanding of the pathological features of the peripheral retina in vascular diseases such as non-perfusion in diabetic retinopathy,12 cross-sectional anatomic information generally remains absent.
The purpose of this study was to obtain high quality, UWF steering-based SD-OCT images of the retinal periphery in order to further elucidate normal peripheral retinal anatomy as well as to better visualize peripheral retinal pathologies. Our efforts to adapt a commercially available device to image the peripheral vitreous, retina, and choroid address the dearth of high quality imaging of the retinal periphery, and may enhance clinical decision-making related to a variety of vitreo-retinal and choroidal disorders.
Methods
The procedures used in this research adhered to the tenets of the Declaration of Helsinki, and Institutional Review Board approval for this study was obtained from the local Ethics Committee. A total of 124 consecutive eyes with previously diagnosed peripheral retinal findings underwent UWF steering-based, SD-OCT imaging from January 2014 to May 2015. Fifty-six eyes with advanced cataract, poorly dilating pupils, poor fixation, and patients with limited cooperation were excluded. Subjects ranged from 18 years to 95 years. SD-OCT imaging was performed by an experienced operator (J.G., ophthalmic photographer) using a single SD-OCT machine (Heidelberg Engineering Co, Heidelberg Germany). A custom dilation and imaging protocol was utilized. There were no additional lenses or device modifications performed in the acquisition of the images. Each patient received 3 sets of dilating drops (phenylephrine 2.5% & tropicamide 1%), 5 minutes apart and was allowed to dilate for 20 minutes prior to imaging. In each case, peripheral retinal scans were performed with a single line scan oriented vertically, horizontally or obliquely (depending on the location and nature of the pathology) with the automatic real-time (ART) set on 100 (Supplemental Figure 1, available at http://aaojournal.org). The lens focus on the SD-OCT device was adjusted from 0 to +18 diopters as dictated by patient axial length in order to achieve a clear near-infrared (NIR) and OCT image. The near-infrared reflectance SLO and SD-OCT images were then registered to the UWF pseudocolor images obtained with the Optos Tx-200 (Optos, California USA) (Supplemental Figure 2, available at http://aaojournal.org). Montage images were composed using photo-editing software (Photoshop version 6.0, Adobe, San Jose, CA).
Results
In all 68 eyes successfully imaged, there was no evidence of macular disease. The vitreoretinal interface and choroidal-scleral boundary was clearly visible in all examined eyes. Nineteen different peripheral findings were imaged in the 68 eyes (Supplemental Table 1, available at http://aaojournal.org). Among these the most prevalent were: retinal hole 26.5% (18/68, Figure 2), cystic retinal tuft 16.1% (11/68, Supplemental Figure 6, available at http://aaojournal.org), typical degenerative senile retinoschisis 13.2% (9/68, Figure 3 and Supplemental Figure 13, available at http://aaojournal.org), pars plana 11.8% (8/68, Supplemental Figure 5, available at http://aaojournal.org), typical cystoid degeneration 8.8% (6/68, Figure 1), retinal tear 7.4% (5/68, Supplemental Figure 10, available at http://aaojournal.org), rhegmatogenous retinal detachment (Supplemental Figures 11 and 12, available at http://aaojournal.org) and ora serrata tooth (Supplemental Figure 5, available at http://aaojournal.org) 5.8% each (4/68 each). Other imaged findings included vortex vein (Supplemental Figure 3, available at http://aaojournal.org), congenital hypertrophy of the retinal pigment epithelium (CHRPE, Supplemental Figure 4, available at http://aaojournal.org), meridional folds (Supplemental Figure 7, available at http://aaojournal.org), lattice degeneration (Supplemental Figure 8, available at http://aaojournal.org), and cobblestone degeneration (Supplemental Figure 9, available at http://aaojournal.org). Nine eyes were found to have more than one peripheral SD-OCT finding. Images and detailed descriptions of the supplemental figures have been included as online-only features (available at http://aaojournal.org).
Figure 2. Retinal hole.
(A) UWF color image with retinal holes, with one hole outlined by the inset. (B, C) Peripheral SD-OCT cross sections of the retinal hole correspond to (D, E) NIR-SLO and an (F) color image with overlaid raster scans (green and yellow arrows). Beneath the hole subretinal fluid (B, C, arrowheads) is present. A partially attached operculum (C, asterisk) is also noted. Vitreous hyper-reflectivity and attachment to the inner retina is present (C, asterisk), while in an adjacent cross-section, no such adhesion is seen (B, asterisks). The retina surrounding the hole contains variable regions of cystoid degeneration and the subretinal space contained hyperreflective material (B, C, arrows). Arrowheads in A-F represent corresponding locations in each panel.
Figure 3. UWF montage of typical degenerative senile retinoschisis with outer retinal hole.
(A) UWF color image of typical degenerative senile retinoschisis. The junction of non-schitic and schitic retina is outlined by the white inset. (B) A montaged UWF SD-OCT cross-section from nasal periphery, through the optic nerve and fovea, to the schitic temporal periphery is registered by the green arrow on the corresponding UWF color image (A). Schisis of the retina at the inner nuclear and outer plexiform layers is seen posteriorly in the temporal macula (B, white arrow) and proceeds all the way to the periphery, with the degree of intraretinal splitting progressively widening posteriorly (white arrowhead) to anteriorly (B, black arrow). (C) Color and (D, F) NIR-SLO images with overlaid raster scans (yellow and green arrows) register the position of additional peripheral SD-OCT cross sections (E, G). An inferotemporal portion of the retina (A, inset; C, D, F, arrowheads) is also analyzed by peripheral SD-OCT, which reveals splitting along the inner nuclear and outer plexiform layers (E, G, white asterisks), and highlights the vitreous interface (G, black asterisk).
Figure 1. Typical cystoid degeneration (TCD).
(A) UWF color image with TCD near the ora serrata, outlined by the inset. (B) Color and (C) NIR-SLO images with overlaid raster scans (green and yellow arrows) demonstrate the positions of adjacent periphera SD-OCT cross sections (D, E). TCD demonstrates saw-tooth patterns comprised of hyporeflective cystoid cavities and broad columns, many of which span the entire thickness of neural retina (D,E, arrows). The delicate vertical columns represent Muller glia and vertically stretched remnants of outer plexiform and inner nuclear layers. Condensed cortical vitreous appears as a moderately reflective layer above the neural retina (D,E, asterisks). Arrows in A-E represent corresponding locations in each panel.
Typical cystoid degeneration
In 6 of 68 eyes, typical cystoid degeneration (TCD) near the ora serrata could be visualized by UWF color and NIR-SLO imaging (Figure 1A-C) and peripheral SD-OCT (Figure 1D,E). On SD-OCT, the TCD region exhibited saw-tooth patterns, which were comprised of hyporeflective cystoid cavities and broad columns, many of which spanned the entire thickness of neural retina (Figure 1D,E, arrows). The nonpigmented epithelium of the pars plana secretes the acid mucopolysaccaride component of the vitreous body, and the condensed cortical vitreous was seen as a moderately reflective layer above the pars plana and peripheral retinal structures. At the apex of the raised surface of the ora serrata pearl, vitreous adhesion to the inner retina was present (Figure 1, asterisks).
Retinal hole
Seventeen retinal holes were identified through UWF SD-OCT (21.8%, 17/68). All holes (Figure 2A) revealed subretinal fluid (Figure 2B, C, arrowheads) within the hole and a detached, partially attached, or attached operculum. In eyes containing a retinal hole with a partially attached operculum, vitreous hyper-reflectivity attached to the inner retina could be visualized (Figure 2C, asterisk), while in an adjacent cross-section, no such adhesion was detected (Figure 2B, asterisk). The retina surrounding the hole had variable regions of cystoid degeneration and the subretinal space contained hyperreflective material (Figure 2B, C, arrows) Examination of the configuration of the retinal holes revealed either an inverted V-shape or a flat-shape (not shown). Holes with a V-shape consistently had an attached or partially attached operculum with vitreous hyper-reflectivity at the inner retinal surface, while those with a flat-shape did not have an attached vitreous hyper-reflectivity or subretinal fluid.
Typical degenerative senile retinoschisis
In an eye with typical degenerative senile retinoschisis, a continuous UWF montage was created, which allowed an unprecedented coverage of high-resolution retinal and choroidal features in a single, 200° image. This was enabled by capture and montaging of serial SD-OCTs from the periphery-to-periphery, through the fovea and optic nerve and to the retinoschisis (Figure 3A). In this montaged UWF SD-OCT image (Figure 3B), schisis of the retinal layers at the inner nuclear and outer plexiform layers was seen posteriorly in the temporal macula (Figure 3B, white arrow) and proceeded all the way to the periphery, with the degree of intraretinal splitting progressively widening posteriorly (white arrowhead) to anteriorly (Figure 3B, black arrow). An inferotemporal portion of the retina (Figure 3A inset; Figure 3C, D, F, arrowheads) was also analyzed by peripheral SD-OCT, which revealed schitic splitting along the inner nuclear and outer plexiform layers (Figure 3E, G, white asterisks), and highlighted the vitreous interface (Figure 3G, black asterisk).
Discussion
In this study, we used a UWF-steering technique to register UWF color images with corresponding peripheral SD-OCT scans, which allowed an unprecedented acquisition of high-resolution cross-sectional structural information of a variety of peripheral retinal entities and pathologies. We also used this approach to assemble a continuous, near 200° SD-OCT montage image from retinal periphery-to -periphery (Figure 3B).
Previously Carrai at al. reported on wide-field SD-OCT imaging in central serous chorioretinopathy (CSCR).14 In their study, photo-editing software was utilized to montage together individual SD-OCT images in eyes with CSCR in order to achieve a single image spanning equator-to-equator horizontally and vertically. Pichi et al. published a similar study as Carrai et al. examining eyes with wet age-related macular degeneration, dry age-related macular degeneration, retinitis pigmentosa, adult exudative polymorphous dystrophy and central serous chorioretinopathy.15 In their study a montage approach was also used to produce a single wide-field SD-OCT image reported as spanning “entire posterior pole spanning ∼200° horizontally and vertically, from equator to equator”, but which did not include the far periphery, as in our images (Figure 3 and Supplemental Figure 12, available at http://aaojournal.org). Finally, Uji and Yoshimura published on ten normal patients using swept source-OCT images that spanned 70° of the retina, in an approach they termed as “extended field imaging.”16 While these prior studies exclusively used a montaged approach to image the retina periphery, except Uji & Yoshimura, whose images were limited to 70°, our study demonstrates a novel technique to image the far retinal periphery using a 30° steerable lens. Furthermore, this ultra-wide field steering approach was used to capture images of features and lesions in the retinal periphery, and when montaged with more posterior, serial SD-OCT images, we could obtain novel 200° cross-sectional views of the retina all the way to the far periphery, which has not previously been described. The montaged images demonstrate clear detail of both the retina and the choroidal scleral boundary.
SD-OCT imaging of the periphery confirmed the close association of the vitreous in association with a variety of peripheral findings. In retinal hole (Figure 2), ora serrata pearl (Supplemental Figure 5, available at http://aaojournal.org), cystic retinal tuft (Supplemental Figure 6, available at http://aaojournal.org), and meridional fold (Supplemental Figure 7, available at http://aaojournal.org), the cortical vitreous was visible and appeared to adhere to the neural retina and exert traction, and in some cases was associated with subretinal fluid. This anatomic association, which we observed in our images, remains consistent with commonly accepted mechanisms that link vitreous traction to peripheral retinal pathologies. We observed other features of the peripheral neural retina that are consistent with previous reports, including relative thinning, or effacement, of all nuclear layers as well as the attenuation of choroidal vessels.8 Our observations regarding cystoid degeneration, which was commonly observed in a variety of peripheral retinal findings including retinal hole (Figure 2), ora serrata pearl (Supplemental Figure 5, available at http://aaojournal.org), cystic retinal tuft (Supplemental Figure 6, available at http://aaojournal.org), and meridional fold (Supplemental Figure 7, available at http://aaojournal.org), are unique to this study and has not yet previously been reported in peripheral SD-OCT studies.
Examination of the montaged images (Figure 3B and Supplemental Figure 12B, available at http://aaojournal.org) revealed clear retinal anatomical detail from the nasal periphery to the temporal periphery including the optic nerve and macula. Figure 3B, a 200° montaged image, demonstrated an example of an eye with temporal early senile retinoschisis with clear intraretinal clefts at the level of the outer nuclear layer extending from the posterior pole out to the far retinal periphery. In Supplemental Figure 12B (available at http://aaojournal.org), a temporal retinal detachment was seen in a 100° montaged image. In this case the nasal periphery was not captured, however the retinal anatomical detail was clear along with the choroid and scleral-choroidal boundary. This image demonstrated a collection of subretinal fluid extending from the periphery towards the posterior pole, threatening the macula. Clearly, peripheral SD-OCT imaging alone and with montaging provides a unique, “10,000 foot” view of peripheral normal retinal anatomy, as well as of peripheral retinal disease, and their relationship to the posterior retina.
There are several limitations to this study and in this technique. First, it is retrospective, and second, the number of eyes analyzed (124, of which 68 could be successfully imaged) remained relatively limited. The frequency of the peripheral findings in this consecutive series does not represent that of the general population due to sampling bias, as many patients whose retinal periphery was imaged were referred for specialized retinal care, such as treatment of a retinal tear. This technique is limited by poor dilation and media opacities (e.g. cataract). In our series of patients without macular disease, approximately 55% of eyes could be successfully imaged with this technique. Since patients are required to fixate on a peripheral light source using the steered technique, patient cooperation can ultimately limit the quality of the acquired images. Thus in a general retina clinic, where maculopathy is frequent, it is likely that fewer than 55% of patients could be successfully imaged. The shortest zero delay line setting on the device has limited the ability to image beyond the pars plana. The mechanical limitations and rotation limitations of the OCT steering head (Heidelberg Spectralis) also limit the extent to which the periphery can be imaged in even well dilated eyes. In devices with a fixed steering head, OCT imaging of the far retinal periphery would likely not be possible.
In summary, our ultra-wide field steering SD-OCT technique provides a novel method for imaging the far peripheral retina, to the pars plana. Furthermore, assembly of montaged, 200° ultra-wide field SD-OCT image provides “birds-eye” view of the periphery in relation to more posterior structures, which may be helpful in identifying potentially novel links between peripheral retinal findings and macular pathologies. The ability to obtain cross-sectional imaging at the far reaches of the retinal periphery is important for a variety of reasons. First, most microscopic, cross-sectional information on retinal peripheral anatomy comes from post-mortem specimens, which does not permit high-resolution, dynamic comparisons over time. Many peripheral entities, such as tumors, meridional folds, cystic retinal tufts, lattice degeneration, retinal holes, retinoschisis with inner and outer layer holes, and even treated or spontaneously scarred retinal tears have a risk of progression toward vision-threatening retinal detachment. Thus, dynamic quantification of specific structural characteristics, such as the change in the amount or distribution of peripheral subretinal fluid over time, by SD-OCT, registered with UWF color image, may aid the clinician in diagnostics (RRD vs senile retinoschisis with inner/outer retinal holes) and decision-making (e.g. additional laser retinopexy treatment for a peripheral retinal break with subretinal fluid). Second, peripheral SD-OCT imaging allows study of the natural history of many these entities, which may permit a better estimation of the risk of these findings progressing toward vision threatening sequelae, as well as their possible correlation to posterior pole/macular and systemic diseases. Third, this approach may improve telemedicine-based triage of peripheral retinal pathologies, especially in remote or resource-poor settings where retinal specialists may not be as readily available.
Supplementary Material
Acknowledgments
This work was supported by the National Eye Institute (K12EY022299) to R.C.R.
Footnotes
Financial Disclosure(s): N.C. received honoraria as a speaker for Optos Plc
Presented at the 2015 Retina Society Meeting, Paris, France
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