ultrahigh-resolution combined coronal optical coherence tomography confocal scanning ophthalmoscope...

12
Summary. Objective: To evaluate clinical images from a pro- totype ultrahigh resolution (UHR) combined coronal optical coherence tomography/confocal scanning ophthalmoscope (OCT/SLO) and to compare them to standard-resolution OCT/SLO images on the same patients. Design: Cross-sectional pilot-study. Participants: Sixty-six eyes of 42 patients with various macular pathologies, such as age-related macular degenera- tion, macular edema, macular hole, central serous retinopa- thy, epiretinal membrane and posterior vitreous traction syn- drome. Methods: Each subject was first scanned with a standard- resolution OCT/SLO that has an axial resolution of ~10 mi- cron. Immediately following, patients were scanned with the prototype UHR OCT/SLO device. The UHR system employs a compact super luminescent diode (SLD) with a 150 nm bandwidth centered at 890 nm, which allows imaging of the retina with an axial resolution of 3 microns. Both coronal and longitudinal OCT scans were acquired with each system, and compared side-by-side. Scan quality was assessed for the observer’s ability to visualize the vitreo-retinal interface and retinal layers – in particular of the outer retina/RPE/choroidal interface, increased discrimination of pathological changes, and better signal intensity. Main outcome measures: Ultrahigh and standard-resolu- tion coronal and longitudinal OCT/SLO images of macular pathologies. Results: In the side-by-side comparison with the commer- cial standard-resolution OCT/SLO images, the scans in the Ultrahigh resolution OCT/SLO images were superior in 85% of cases. Relatively poor quality images were attributed to lower signal-to-noise ratio, limited focusing, or media opaci- ties. Several images that had a better signal intensity in the standard-resolution OCT/SLO system were found to show more retinal detail in the UHR system. In general, intraretinal layers in the UHR OCT/SLO images were better delineated in both coronal and longitudinal scans. Enhanced details were also seen in the outer retina/RPE/choroidal complex. The UHR OCT/SLO system produced better definition of morphological changes in several macular pathologies. Conclusions: Broadband SLD-based UHR OCT/SLO offers a compact, efficient, and economic enhancement to the currently available clinical OCT imaging systems. UHR OCT/SLO imaging enhanced the quality of the OCT C-scans, facilitated appreciation of vitreo-retinal pathologies, and im- proved sensitivity to small changes in the retina, and the outer retina/RPE/choroidal interface. Key words: OCT ophthalmoscope, OCT/SLO, ultrahigh resolution OCT, coronal OCT. Introduction Optical Coherence Tomography (OCT) has emerged as an important diagnostic imaging tool in ophthalmology. OCT is similar to ultrasound, but uses low-coherent light instead of sound. The “optical” echo delay time and the magnitude of the reflected and backscattered light are measured through a phenomenon called interference [1, 2]. OCT makes in vivo “optical” biopsies, providing histology-like cross-sectional images of the tissue under investigation, in our case the human retina. Most OCT systems reported to date, both time-domain [3–6] and spectral domain [7–9] are only capable of acquir- ing real time cross-sections of the human retina in a plane containing the eye optical axis. This translates in image ac- quisition by fast scanning in the axial direction, i. e. depth, and scanning at a slower pace in the transverse direction [3]. These cross-sections are referred to as longitudinal scans or OCT B-scans. In addition to the capability of B-scan acquisition by fast scanning in the transverse direction and slow scanning in depth, the en-face OCT technique also allows for the acquisi- tion of cross-sections of the retina in a plane perpendicular to the eye optical axis [10, 11]. In other words, scanning can be performed parallel to the retinal surface. This scanning regime offers a similar perspective as biomicroscopy, scan- ning laser ophthalmoscopy (SLO) or confocal microscopy [10, 12, 13]. The time-domain OCT instruments reported in this article combine high resolution OCT cross-sections with simultaneous corresponding confocal scanning “laser” oph- Ultrahigh-Resolution Combined Coronal Optical Coherence Tomography Confocal Scanning Ophthalmoscope (OCT/SLO) : A pilot study R. B. Rosen 2 , M. E. J. van Velthoven 1,2 , P. M. T. Garcia 2 , R. G. Cucu 3 , M. D. de Smet 1 , T. O. Muldoon 2 , and A. Gh. Podoleanu 3 1 Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands 2 Advanced Retinal Imaging Laboratory, New York Eye and Ear Infirmary, New York, NY, USA 3 Applied Optics Group, University of Kent, Canterbury, UK Spektrum Augenheilkd (2007) 21/1: 17–28 DOI 10.1007/s00717-007-0182-4 © Springer-Verlag 2007 Printed in Austria Spektrum der Augenheilkunde

Upload: kent

Post on 25-Nov-2023

0 views

Category:

Documents


0 download

TRANSCRIPT

Summary. Objective: To evaluate clinical images from a pro-totype ultrahigh resolution (UHR) combined coronal optical coherence tomography/confocal scanning ophthalmoscope (OCT/SLO) and to compare them to standard-resolution OCT/SLO images on the same patients.

Design: Cross-sectional pilot-study.Participants: Sixty-six eyes of 42 patients with various

macular pathologies, such as age-related macular degenera-tion, macular edema, macular hole, central serous retinopa-thy, epiretinal membrane and posterior vitreous traction syn-drome.

Methods: Each subject was first scanned with a standard-resolution OCT/SLO that has an axial resolution of ~10 mi-cron. Immediately following, patients were scanned with the prototype UHR OCT/SLO device. The UHR system employs a compact super luminescent diode (SLD) with a 150 nm bandwidth centered at 890 nm, which allows imaging of the retina with an axial resolution of 3 microns. Both coronal and longitudinal OCT scans were acquired with each system, and compared side-by-side. Scan quality was assessed for the observer’s ability to visualize the vitreo-retinal interface and retinal layers – in particular of the outer retina/RPE/choroidal interface, increased discrimination of pathological changes, and better signal intensity.

Main outcome measures: Ultrahigh and standard-resolu-tion coronal and longitudinal OCT/SLO images of macular pathologies.

Results: In the side-by-side comparison with the commer-cial standard-resolution OCT/SLO images, the scans in the Ultrahigh resolution OCT/SLO images were superior in 85% of cases. Relatively poor quality images were attributed to lower signal-to-noise ratio, limited focusing, or media opaci-ties. Several images that had a better signal intensity in the standard-resolution OCT/SLO system were found to show more retinal detail in the UHR system. In general, intraretinal layers in the UHR OCT/SLO images were better delineated in both coronal and longitudinal scans. Enhanced details were also seen in the outer retina/RPE/choroidal complex. The UHR OCT/SLO system produced better definition of morphological changes in several macular pathologies.

Conclusions: Broadband SLD-based UHR OCT/SLO offers a compact, efficient, and economic enhancement to the currently available clinical OCT imaging systems. UHR OCT/SLO imaging enhanced the quality of the OCT C-scans, facilitated appreciation of vitreo-retinal pathologies, and im-proved sensitivity to small changes in the retina, and the outer retina/RPE/choroidal interface.

Key words: OCT ophthalmoscope, OCT/SLO, ultrahigh resolution OCT, coronal OCT.

IntroductionOptical Coherence Tomography (OCT) has emerged as an important diagnostic imaging tool in ophthalmology. OCT is similar to ultrasound, but uses low-coherent light instead of sound. The “optical” echo delay time and the magnitude of the reflected and backscattered light are measured through a phenomenon called interference [1, 2]. OCT makes in vivo “optical” biopsies, providing histology-like cross-sectional images of the tissue under investigation, in our case the human retina.

Most OCT systems reported to date, both time-domain [3–6] and spectral domain [7–9] are only capable of acquir-ing real time cross-sections of the human retina in a plane containing the eye optical axis. This translates in image ac-quisition by fast scanning in the axial direction, i. e. depth, and scanning at a slower pace in the transverse direction [3]. These cross-sections are referred to as longitudinal scans or OCT B-scans.

In addition to the capability of B-scan acquisition by fast scanning in the transverse direction and slow scanning in depth, the en-face OCT technique also allows for the acquisi-tion of cross-sections of the retina in a plane perpendicular to the eye optical axis [10, 11]. In other words, scanning can be performed parallel to the retinal surface. This scanning regime offers a similar perspective as biomicroscopy, scan-ning laser ophthalmoscopy (SLO) or confocal microscopy [10, 12, 13]. The time-domain OCT instruments reported in this article combine high resolution OCT cross-sections with simultaneous corresponding confocal scanning “laser” oph-

Ultrahigh-Resolution Combined Coronal Optical Coherence Tomography Confocal Scanning Ophthalmoscope (OCT/SLO) : A pilot study

R. B. Rosen2, M. E. J. van Velthoven1,2, P. M. T. Garcia2, R. G. Cucu3, M. D. de Smet1, T. O. Muldoon2,and A. Gh. Podoleanu3

1 Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands2 Advanced Retinal Imaging Laboratory, New York Eye and Ear Infirmary, New York, NY, USA3 Applied Optics Group, University of Kent, Canterbury, UK

Spektrum Augenheilkd (2007) 21/1: 17–28DOI 10.1007/s00717-007-0182-4

© Springer-Verlag 2007Printed in Austria

Spektrumder Augenheilkunde

18

thalmoscopic (OCT/SLO) images providing pixel-to-pixel registration between cross-sectional thin slices and retinal surface features [11, 14]. The en-face cross-sections are re-ferred to as coronal or transversal scans or OCT C-scans.

The currently available, standard-resolution, time-domain OCT systems (Stratus OCT, Carl Zeiss Meditec Inc, Dublin, CA, USA and OCT/SLO, Ophthalmic Technologies Inc, To-ronto, Canada) use a super luminescent diode (SLD) with a central wavelength of 820 nm and a bandwidth of ~ 20 nm. This offers an ideal axial image resolution in the retina of 8–10 micron [4, 14]. Axial resolution is inversely proportional to the bandwidth of the light source being used. A Ti:sap-phire, femtosecond laser with a central wavelength of 800 nm and a bandwidth up to 165 nm, can be used as a light source in an ultrahigh resolution OCT (UHR-OCT) system that can provide a threefold higher axial resolution in comparison to standard resolution OCT systems. However, the Ti:sapphire, femtosecond laser light source used in the first UHR-OCT prototype is expensive, complex and relatively high mainta-nence. More compact and less expensive alternatives have been developed [15, 16]. In this pilot-study a prototype Ul-trahigh-Resolution (UHR) OCT/SLO, based on a low-cost, compact, broadband SLD (bandwidth 150 nm centered at 890 nm), was used to scan patients with various macular pa-thologies. This prototype UHR OCT/SLO provides an image resolution of 3.2 µm in the retina [31].

This article will attempt to assess the value of the im-proved resolution in both the OCT B- and C-scans of this UHR OCT/SLO system. First, the ability to distinguish intra-retinal layers in both scanning modes was evaluated, assess-ing delineation of the ganglion cell layer (GCL), the exter-nal limiting membrane (ELM) the photoreceptor inner/outer segment complex (IS/OS), retinal pigment epithelium (RPE) and choriocapillaris (CC), for evidence of improvement. Sec-ond, this UHR OCT/SLO was utilized to compare its OCT scans with those of the standard-resolution OCT/SLO. It is hypothesized that the UHR OCT/SLO might not only serve as an aid in the interpretation of these coronal sections, but that it might also provide additional information in macular pathologies that could help to elucidate the pathogenesis and, ultimately, assist in the management of these diseases.

MethodsBetween August and December 2005 patients with various retinal diseases who were seen in the Retina Center of the New York Eye and Ear Infirmary (NYEEI, New York, NY, USA), and who were eligible to participate in this pilot study, were included. The study was reviewed and approved by the institution review board of the NYEEI and was conducted in compliance with HIPPAA-regulations.

The prototype UHR OCT/SLO system is based on a low-cost, compact, broadband SLD (Broadlighter D-890, Super-lum Diodes Ltd, Moscow, Russia). This SLD is built out of two individual SLDs with overlapping spectra resulting in a spectral full width at half maximum bandwidth (FWHM) of 150 nm centered at 890 nm. The axial resolution of the sys-tem is 3.4 µm in air, and 3.2 µm in the retina [31]. The basic set-up is similar to that of the previously reported standard-resolution OCT/SLO system (Fig. 1) [10, 11, 14]. However, in order to preserve the axial resolution given by the broad-band light source, polarization and dispersion imbalances in-duced by the system’s optical components and the refractive media of the eye have to be matched. This can be achieved

by inserting blocks of matching glass type in the reference arm and using fiber polarization controllers. To further com-pensate for dispersion induced by the vitreous, a 48 mm long (double the average eye length) water-cuvette is placed in the reference arm of the interferometer [31]. For 1 mW optical incident power on the target, the sensitivity of the system was estimated to be higher than 98 dB. The incident power on the cornea is less than 1mW, which is within the ANSI standard for safe retinal exposure for line scanning at 1 kHz [17].

Fig. 1. Schematic of the instrument (From Cucu RG [31])

As reported previously [10, 11, 14], an OCT scan is si-multaneously acquired with a confocal ophthalmoscopic im-age. In the UHR OCT/SLO system this is done by inserting a highly reflective broadband beam-splitter to divert part of the back reflected light from the retina to the confocal chan-nel detector. Raster scanning is based on flying spot T-scans, scanning fast in the X,Y-plane. By moving the translation stage at a slower pace in depth, consecutive coronal scans are acquired. OCT B-scans are acquired by scanning at a fixed X,Y-coordinate while moving along the Z-axis in depth [10, 11, 14]. Both the confocal and OCT signals are fed into a frame grabber attached to a computer, and depicted as gray-scale images. Both the prototype and the commercial model scan at a rate of 2 frames per second in the OCT C-scan mode and 1 frame per second in the OCT B-scan mode. The scan angle in the prototype is 20°, while for the commercial model it is 24°; this is roughly equivalent to a 7.5 and 8 mm scan length respectively. In the OCT B-scan mode the commer-cial device scanned 1.125 mm in depth, while the prototype scanned 0.75 mm in depth. While this is adjustable, it is as-sociated with loss of axial resolution (in the prototype). The simultaneously acquired confocal and OCT images are dis-played as pairs of 512 × 512 pixels. Both machines acquire a topographic stack, consisting of 100 consecutive OCT C-scans (256 × 256 pixels) at a 10° scan angle (~ 4 mm), in 2 seconds.

Study patients were recruited from patients scanned with the first generation commercial OCT/SLO (Ophthalmic Tech-nologies Inc., Toronto, Canada) which uses a SLD with a cen-tral wavelength of 820 nm and a 20 nm bandwidth, resulting

19

in an axial resolution of ~ 10 micron. Patients were eligible if the scan on the commercial model was of good quality. In ad-dition, due to technical limitations in the prototype, patients could only participate if they had refractive errors between –4D and +3D.

Images from both devices were compared side-by-side. Differences in quality were assessed based on a set of fixed criteria consisting in: (1) visualization of the vitreo-retinal interface, (2) delineation of retinal layers, (3) appreciation of detail in the outer retina/RPE/choroidal interface, (4) dis-crimination of pathological changes, and (5) signal intensity. Based on these criteria the operators assessed the scans as poor, adequate or good.

Results Over three months, 42 patients (66 eyes) with a mean age of 61.7 years (SD ± 14.8 yrs), were scanned using both OCT/SLO systems. Patients had the following macular patholo-gies: age-related macular degeneration (AMD, 21 eyes), dru-sen (2 eyes), choroidal nevus (3 eyes), cystoid macular edema (CME, 5 eyes), central serous retinopathy (CSR, 8 eyes), dia-betic retinopathy (DRP, 4 eyes), epiretinal membrane (ERM, 3 eyes), macular hole (MH, 3 eyes), posterior vitreous detach-ment (PVD, 2 eyes), uveitis (2 eyes). Idiopathic juxtafoveal telangiectasis (IJT), unilateral cone/rod dystrophy, geographic atrophy, unilateral central retinal vein occlusion, unilateral optic pit maculopathy and idiopathic poly poidal choroidal vasculopathy (IPCV) were each scanned in 1 patient. Four fellow eyes were normal.

Scans rated as Good or Acceptable were obtained in 97% of patients examined with the prototype UHR OCT/SLO. In the side-by-side comparison, UHR OCT/SLO images were judged better than the standard-resolution OCT/SLO images in 85% of cases. In the 15% where the standard resolution imaging prevailed, the issue appeared to be reduced signal-to-noise ratio in the UHR scans despite preservation of en-hanced retinal layers. In a few cases with macular edema, the depth range of the UHR OCT/SLO had to be maximized to scan the full extent of the retinal elevation, resulting in some

loss of axial resolution. In most cases the 0.75 mm was suf-ficient to scan the affected macular area in the OCT B-scan.

The first example included here of a 29 year old normal volunteer demonstrates the finer grain appearance of images taken using the UHR OCT/SLO compared to the standard resolution system (Figs. 2 and 3). The intersection of the cur-vature of the eye with the flatter arc of the scan ray produces slices through the stack of retinal layers which appear more ellipsoidal than circular due the oblique angle of encounter at the edge of the coronal frame as opposed to the perpendicular angle of encounter centrally. The improved resolution of the UHR system allows for a better appreciation and interpreta-tion of structures in deeper layers of the retina especially in the coronal C-scans. Within the inner retina, the various lay-ers, such as the GCL, inner and outer plexiform and nuclear layers, are better appreciated than in the standard-resolution OCT/SLO, where these layers appear more confluent due to overlapping reflectivities, echoes, and the overall grainy quality of the scan.

The visualization of the outer retina/RPE interface struc-tures appears to improve with the increase in the axial reso-lution. Smaller structures such as ELM can be appreciated in the UHR OCT/SLO, which have rarely been documented in a standard-resolution OCT C-scan. Furthermore, we ob-served three hyper-reflective bands that formed the outer retina/RPE/choriocapillaris complex, where standard OCT techniques only show two. The first hyper-reflective layer in the outer retina band is thought to correspond to the IS/OS of the photoreceptor layer. In our images, the second band which is usually seen as one thick, slightly irregular band, is actually made up out of two separate bands. We suspect that the first of these two bands corresponds to the photoreceptor outer segments intertwined with the digits of the RPE cells, while the second layer corresponds to the cell bodies of the RPE [18]. A thin dark band between the RPE and chorio-capillaris is also more consistently delineated with the higher resolution.

With the improved quality of the OCT B- and C-scan images, it becomes easier to localize abnormalities, and the

A A

B B

20

Fig. 2. Normal Eye. A Normal – Commercial OCT/SLO – Longitudi-nal scan with corresponding SLO (lower right). B Normal – commercial OCT/SLO – OCT C-scan 1. SLO (left) shows surface features while cor-responding C-scan OCT shows central dark circle of the foveal depres-sion surrounded by more peripheral aspects of the fundus bowl. A slight tilt results in only part of the nerve fiber layer (bright crescent) being cap-tured. The bright lines in the corners of the image represent the RPE re-gion. C Normal – commercial OCT/SLO – OCT C-scan 2 highlights the retinal vessel below due to tilt. The superior vessel is dark due to shadow-ing caused by the depth of the scan being deeper in that area. D Normal – commercial OCT/SLO – OCT C-scan 3 cuts across RPE layer more obliquely so that it appears wider. Dark shadow images of the retinal vessels are seen and choroidal pattern is evident in the corners outside of the RPE ring. E Normal – commercial OCT/SLO – OCT C-scan 4 high-lights the RPE and surrounding choroid. The small dark spot is the floor of the foveal depression above the hyporeflective photeceptor region. The double ring which forms an “8” is an artifact produced by shifting tilt which occurred during the scan. F Normal – commercial OCT/SLO – OCT C-scan at the level of the choroid with a central teardrop shaped hyper-reflective spot at the level of the RPE. A dark border divides the area from the surrounding choroids. Shadows of the arcades are seen.

C

D

E

F

C

D

E

F

Fig. 3. Normal Eye – High resolution. A. Normal – High Resolution Longitudinal OCT/SLO demonstrating enhanced definition of internal retinal layers. B Normal – High Resolution OCT/SLO – OCT C-scan 1 demonstrates a bright ring within the foveal depression circle corre-sponding the nerve fiber level. The brightness of the vessels suggests that the level of this scan approximates the depth of the vessels causing their high reflectance. C Normal – High Resolution OCT/SLO – OCT C-scan 2 revealing a smaller foveal circle as the scan level deepens to the level of the vascular arcades. D Normal – High Resolution OCT/SLO – OCT C-scan 3 deep to the floor of the foveal depression. The RPE region dem-onstrates multiple layers within the bright region separating the retina and choroids. The innermost line appears to represent the IS/OS junction. The middle line includes the OS/RPE junction with the outermost line being the RPE cell bodies. The hyporeflective region external between the RPE and the choriocapillaris likely represents Bruch’s membrane.E Normal – High Resolution OCT/SLO – OCT C-scan 4 further high-lights the details of the RPE region also showing a dark line between the RPE the choroid in the region of Bruch’s membrane. F Normal – High Resolution OCT/SLO – OCT C-scan slice is deeper within the choroids. The bright circle in the middle is the RPE region surrounded by the darker line in Bruch’s membrane region.

21

extent of retinal pathologies is better appreciated. In case of subtle retinal or subretinal changes, the images were often key elements in the diagnostic process. A number of patho-logic cases including macular hole, vitreo-macular traction, epiretinal membrane, macular degeneration, and macular telangiectasia are presented in this report to demonstrate the point.

In Fig. 4B and D, UHR OCT C-scan of a patient with a full thickness MH is shown beside the OCT C-scan made with the

Fig. 3. G Normal – High Resolution OCT/SLO Topographic thickness map with vertical and horizontal OCT cross-sections. The numbers dis-played represent average thickness of each individual square. The retinal thickness data is overlaid upon the vascular pattern of the corresponding SLO. H Normal – High Resolution OCT/SLO Topographic thickness map overlaid upon the corresponding SLO image (wide angle)

G

H

G

H

Fig. 2. G Normal – Commercial OCT/SLO Topographic Thickness Map with vertical and horizontal OCT reconstructions. Details of the retinal vascular pattern help to localize the measurement grid. The numbers represent the average thickness for the individual square. The actual thickness at any point can be determined in the live image by moving the cursor over the map. The longitudinal OCT on the right corresponds to the vertical green line. The OCT beneath the map corresponds to the horizontal blue line. The blue and green lines can be moved in the live image to reveal the OCT images at any location on the map. H Normal – Commercial OCT/SLO Topographic Thickness Map in zoomed out mode showing the location of the measured grid on the SLO image. A slight disparity in the vessel alignment is seen due to uncorrected shift in tilt

standard-resolution system. The frames are taken at the same level. More detailed information is visible in the UHR scan taken in mid retina: small septae between the cystic spaces within the rim of the macular hole, and the peripheral border of these cystic changes is more clearly demarcated.

In the OCT B-scans (Fig. 4A and C) the MH is clearly defined in both machines. The operculum is better visualized with the standard-resolution OCT/SLO. This discrepancy is due to the limited depth range of the UHR system. In both machines the edematous rim of the hole is appreciated, but the cystic spaces and the separating septae in the inner nu-clear layer are better defined in the UHR scan. At the base of the macular hole, irregularities are seen on the RPE surface which can also be seen clinically.

22

The patient in Fig. 4 had asymptomatic posterior vitreous traction in the fellow eye (Fig. 5). Coronal scans are compa-rable in both machines, with a slightly better delineation of intraretinal layers in the UHR scan. The longitudinal scans show the vitreo-macular traction band in both the standard-

resolution and UHR image. The signal intensity of the vitre-ous traction is more distinct in the standard-resolution scans, but this again can be partly attributed to the limited depth range in the UHR system. In both machines, intraretinal cys-tic changes are seen in the outer nuclear layer. The spaces are

A

B

C

D

Fig. 4. Patient with a Macular Hole and Posterior Vitreous Traction in the fellow eye. A Macular hole – Commercial OCT/SLO demonstrates hyaloid separation with overlying operculum. Edges of the hole suggest swelling of retinal layers while the base of the hole shows excrescenses. B Macular hole – Commercial OCT/SLO – OCT C-scans display faint concentric pattern of cystic change surrounding the hole and deeper layers proceeding outward towards the edge of the image. The SLO (left) shows double ring appearance on the retinal surface. C Macular hole – High Resolution OCT/SLO reveals delicate cystic changes within the middle retinal layers and well defined edges of hole. D Macular hole – High Resolution OCT/SLO – OCT C-scan reveals septae of surrounding cysts and additional intra-retinal layers

A

B

C

D

Fig. 5. A Posterior Vitreous Traction – Commercial OCT/SLO demonstrating attachment of the hyaloid to the fovea tractional cystic changes. B Poste-rior Vitreous Traction – Commercial OCT/SLO – OCT C-scan is slightly tilted with central cluster of cysts surrounded by intraretinal layers and partial RPE ring. C Posterior Vitreous Traction – HR OCT/SLO shows the attachment of the hyaloid less distinctly at the edge of the depth range of the system. D Posterior Vitreous Traction – HR OCT/SLO – OCT C-scan is slightly less tilted and shows finer internal retinal features. A patch of nerve fiber layer is seen in the lower right due to the tilt which also introduces a discontinuity in the RPE ring

23

more clearly defined in the UHR images. The intact ELM and junction of IS/OS of the photoreceptors clarifies the fact that visual acuity was still normal.

Images of a patient with wet AMD are shown in Fig. 6. The confocal image on the left side in the OCT C-scan (Fig. 6B and E) shows a large area of a scarred choroidal neovas-cular membrane (CNV). The OCT C-scans on both systems nicely show the irregular extent of the scarring. The enhanced resolution of the UHR system shows a better delineation of

intraretinal layers and their relative orientation within the elevated retina.

OCT B-scans (Fig. 6A and D) show the scarred CNV lesion at the level of the RPE, with destruction of the outer retinal layers. Due to atrophic changes in the retina and RPE, there is better visualization of the choroidal vessels underneath the RPE/CNV complex in some areas. A strik-ing finding in the UHR OCT B-scan is the very thin, but hyper reflective layer running under the CNV. While its size

Fig. 6. Patient with a choroidal neovascularization in Age-related Macular Degeneration. A Wet AMD – Commercial OCT/SLO demonstrates extensive subretinal fibrosis with cystic features. Inner retinal layer has limited definition. B Wet AMD – Commercial OCT/SLO – OCT C-scan shows distur-bance at the level of the RPE which distorts the overlying retina and obscures details of the layers. C Wet AMD – Commercial OCT/SLO Topographic retinal thickness map shows generalized thickening of the retina with preservation of the foveal depression. Irregular thickening of the RPE region due to fibrotic deposition has resulted in some fluctuations in the algorithm’s choice of retinal boundary. The software permits manual editing of the bound-ary which has yet not been done in this example. D Wet AMD – High Resolution OCT/SLO is able to distinguish inner retinal layers and some detail within the subretinal fibrotic debris. E Wet AMD – High Resolution OCT/SLO – OCT C-scan also reveals more distinct detail in the retina overlying the neovascular disturbance violating the RPE. F Wet AMD – High Resolution OCT/SLO Topographic Retinal Thickness Map shows similar areas of diffuse retinal thickening more discreetly

C F

A

B

D

E

24

and location appears consistent with Bruch’s membrane, its variable appearance across scans suggests some form ofartifact.

Images of a patient with confluent drusen are shown in Fig. 7. The OCT C-scans (Fig. 7B and E) in this patient show widespread, variably sized drusen (actually the RPE eleva-tions caused by the deposits) that are confluent in some ar-eas. The drusen appear to be homogeneous in nature in the standard-resolution OCT/SLO scan, but are seen to have a lower reflectivity within the confinements of the RPE in the

UHR scan. The smaller drusen seem to have a higher reflec-tive contents than the larger ones.

The OCT B-scans (Fig. 7A and D) clearly show the vari-ous sized RPE elevations caused by the deposits. Like in the OCT C-scans, the UHR image shows that the contents of the drusen are of variable reflectivity and hardly cast any shadow onto the deeper layers. This is different from a serous RPE detachment, which has optically empty contents attenuating the signal to the underlying structures. Closer examination of the longitudinal images shows that there is an abrupt crossing

C F

Fig. 7. Patient with confluent drusen. A Confluent Drusen – Commercial OCT/SLO demonstrates variable size and configuration of drusen cluster along with some distinction of RPE region layers and those of overlying retina. B Confluent Drusen – Commercial OCT/SLO – OCT C-scan reveals some variability to the core and placement of the individual drusen. C Confluent Drusen – Commercial OCT/SLO Topographic Retinal Thickness Map con-firms the preservation of normal macular thickness despite the lumpiness of the drusen cluster which is evident in the map. D Confluent Drusen – High Resolution OCT/SLO reveals finer features of drusen and their effect on the overlying retina. Multiple layers can be seen over the actual drusen as well as in the inner retina. E Confluent Drusen – High Resolution OCT/SLO – OCT C-scan reveals variable internal structures within drusen. F Confluent Drusen – High Resolution OCT/SLO Topographic Retinal Thickness Map shows light and dark pattern of underlying drusen as well as disturbance of overlying retina. The red band at the bottom of the image is artifactual

A

B E

D

25

between the bottom of the drusen and the underlying chorio-capillaris. Under certain drusen, Bruch’s membrane can be distinguished as a thin hypo reflective layer. Relative to the standard-resolution OCT B-scan, the overlying IS/OS and the ELM are clearly seen in the UHR scan and follow the con-tours of the drusen.

Images of a patient with an epiretinal membrane are shown in Fig. 8. In both machines, the epiretinal membrane

is seen in both longitudinal and coronal sections. However, the subtle attachments between the membrane and the retina are better appreciated in the longitudinal sections using the UHR system. In the standard-resolution OCT B-scan a cystic area can be easily mistaken for an intraretinal cyst (Fig. 8A), while the UHR scan clearly shows that this area corresponds to a spacing between two surface wrinkles caused by the trac-tional ERM (Fig. 8D). The enhanced resolution of the UHR

C F

Fig. 8. Patient with an epiretinal membrane. A Epiretinal membrane – Commercial OCT/SLO shows good separation of surface details as well as inner retinal layers. Note the flattening of the perifoveal retinal surface and the constriction of the foveal depression contributing to the peseudohole appearance on fundoscopy. B Epiretinal membrane – Commercial OCT/SLO – OCT C-scan demonstrates radiating folds of a contracting membrane. The image is slightly tilted back superiorly as indicated by the dark area below which is the vitreous and retina interface. The SLO image shows the more superficial appearance of the membrane. The smaller dark spot surrounded by the white ring represents the foveal depression surrounded by the contracting membrane. C Epiretinal membrane – Commercial OCT/SLO Topographic Retinal Thickness Map demonstrating the diffuse retinal thickening and surface distortion in relation to the macular vascular pattern. D Epiretinal Membrane – High Resolution OCT/SLO showing the pinch-ing of the surface in relation to the underlying retinal layers. E Epiretinal Membrane – High Resolution OCT/SLO – OCT C-scan clearly delineates the pleats in the nerve fiber layer produced by the contracting membrane F Epiretinal Membrane – High Resolution OCT/SLO Topographic Retinal Thickness Map shows the relationship between the surface wrinkling and measurement of the tractional retinal edema. The redband below is artifactual

A

B E

D

26

B-scan also shows traction on the delicate outer retina within the fovea, indicated by the increased spacing between ELM, IS/OS and RPE.

The extent of an ERM is better appreciated in coronal cuts (Fig. 8B and E). Characteristic of ERMs are radial lines extending from the traction’s epicenter. They are better ap-preciated on coronal scans from either machines as compared to biomicroscopic examination.

A case of idiopathic juxtafoveal telangiectasia is shown in Fig. 9. In this patient with IJT, an ILM drape [19], was bet-ter appreciated in the longitudinal UHR OCT/SLO images. The hyper-reflective area corresponds to an intraretinal vas-cular anomaly, scattering and absorbing much of the incident light, blurring underlying structures. This is similar in both machines. The OCT B-scans from both systems show a well preserved photoreceptor layer. Only in the direct vicinity of

C F

Fig. 9. Patient with idiopathic juxtafoveal telangiectasis. A Macular Telangiectasia – Commercial OCT/SLO shows highly reflective perifoveal lesion with cystic change beneath the foveal floor. B Macular Telangiectasia – Commercial OCT/SLO – OCT C-scan taken at the level of the highly reflective pigmentary invasion of the retina. C Macular Telangiectasia – Commercial OCT/SLO Topographic Retinal Thickness Map shows the thinning of the retinal over the vascular lesion. D Macular Telangiectasia – High Resolution OCT/SLO shows more details of the anatomic changes produced by the vascular lesion. The shadowing beneath hyper-reflective pigmentary invasion produces less distortion and the involvement of specific intraretinal layers can be better appreciated. E Macular Telangiectasia – High Resolution OCT/SLO – OCT C-scan taken at the level of the highly reflective pigmentary in-vasion demonstrates a cystic structure which may be part of the vascular anomaly. The backward tilt of the upper part of the scan shows the multilayered structure of the RPE region above and a wisp of the nerve fiber layer toward the lower right of the image. F Macular Telangiectasia – High Resolution OCT/SLO Topographic Retinal Thickness Map detailing the vascular distortion towards the lesion. The algorithym again identifies the hyper-reflective lesion as the RPE boundary and portrays the area of the lesion as being thin despite the appearance in the OCT B-scan shown below. The red band below is also artifact produced at the edge of the high-speed stack

A

B E

D

27

the intraretinal vessel anomaly, detail is lost. The OCT C-scans show the extent of the IJT as a paint-spot pattern.

ConclusionThese preliminary results show that a low-cost, compact, broadband SLD-based UHR OCT/SLO system offers an effi-cient and affordable enhancement to the currently available time-domain clinical OCT imaging systems. In general, UHR OCT/SLO imaging produces better appreciation of the vit-reo-retinal interface and underlying retinal layers. The UHR OCT/SLO scans also provide more detail within the outer retina/RPE/choroidal complex, showing a triple hyper reflec-tive band instead of the usually demonstrated double hyper-reflective band [18]. The enhanced resolution in the UHR OCT/SLO images also aided in the understanding and inter-pretation of the standard-resolution OCT C- and B-scans.

Recent reports on UHR OCT imaging all demonstrate enhanced visualization of intraretinal layers and a better ap-preciation of the complex anatomical relationship between photoreceptors, RPE and choriocapillaris [6, 19–24]. In dis-eases affecting the photoreceptors, this may be particularly useful [20, 23]. In this respect, our UHR imaging shows re-sults similar to those published so far, but the fast scanning in the XY plane used in the OCT/SLO systems allows for a better preservation of lateral resolution. This preserved lateral resolution translates in a subjectively higher image resolu-tion. For example, a triple hyper-reflective band is visible at the level of the outer retina. This could only be demonstrated by Sander et al. [18] in the standard-resolution Stratus OCT using multiple scan averaging. The first hyper-reflective band corresponds to the intersection of photoreceptors’ IS/OS. The first part of double band visualized underneath the IS/OS band most likely corresponds to the photoreceptor outer seg-ments entangled by the melanin-containing digits of the RPE cells, while the second part may correspond to the RPE cell bodies themselves.

The OCT/SLO system is unique in producing simultane-ously acquired high quality confocal fundus images and high-resolution coronal OCT images. Recent reports have demon-strated the value of the realtime, high resolution overview of the area of interest that OCT C-scans provide [14, 25, 26]. OCT C-scans facilitate identification of focal changes with their circumspect overview and help differentiate pathologi-cal structures from surrounding healthy tissue. The high reso-lution coronal views of the retina produced by this system were much easier to interpret than standard resolution OCT C-scans [14]. Small changes in the coronal scans from the standard-resolution system can easily be misinterpreted as speckle noise. The finer resolving power in the UHR system helps to distinguish the nature these small changes enough to label them abnormal or not.

The OCT C-scan mode is a dynamic imaging modality. The “live” video feed of C-scan frames taken at various depths of the retina is especially useful for rapid identification of path-ological lesions. Fine features within individual retinal layers and thickness assessments of these layers are probably bet-ter appreciated in well-centered single, frozen OCT B-scans. Since both OCT/SLO systems are designed to capture B-scan mode images at any given angle, small eccentric lesions de-tected by coronal scanning can be re-imaged to optimize detail.

This prototype (UHR) OCT/SLO system is also one of the fastest time-domain systems for the acquisition of 3D rendered stacks. Both systems acquire a stack of 100 con-

secutive C-scans in 2 seconds at a 10° angle (~ 4mm). Other high speed OCT systems recently reported either acquire a 3D stack with fewer frames at a faster rate [27] or acquire a 3D stack at higher pixel density, but require a 3-fold longer acquisition time [9]. The 3D stack in the OCT/SLO system is mainly used for measuring retinal thickness and to moni-tor variation in thickness over time. When monitoring retinal thickness over time in an individual patient, the stack’s resolu-tion is less critical than is alignment and the number of actual data points. In this regard, the (UHR) OCT/SLO system has several advantages over OCT systems based on longitudinal scanning. First, the simultaneously acquired confocal image can be used as a reference image to align the individual OCT C-scan frames within the stack. Second, the 3D rendering is built up from coronal frames instead of longitudinal frames, providing a much more fluent and non-transparent slide-through model of the area of interest in comparison to the “transparent glass model” introduced by Schmidt-Erfurth et al. [9]. Finally, the retinal thickness maps made by the Stratus OCT have proven to be reliable and reproducible [28, 29], but these are based on just six radial lines consisting of 512 A-scans. All remaining data points are interpolated. Slight fixa-tion errors can significantly decrease the reliability [30], and this approach does not allow for detailed surface thickness analysis. In the (UHR) OCT/SLO system the whole mapping area is scanned, eliminating the need for interpolation, thus providing more detailed thickness measurements and allow-ing focal changes in thickness to be appreciated.

Certain limitations of the UHR-OCT/SLO system are in-herent to a prototype set-up. The commercial OCT/SLO sys-tem is still easier to use (due to its built-in automatic focus-ing feature) and can accommodate a larger range of patient refractive errors (–18D to +25D compared to –4D to +3D for the prototype) and B-scan axial ranges (1.125 mm com-pared to 0.75 mm for the prototype). However, it is possible to overcome these limitations by modifying the design of a commercial OCT/SLO system to support the high bandwidth of a broadband SLD. This would involve essential dispersion imbalance compensation and polarization state matching.

In summary, we demonstrated an affordable enhancement of clinical OCT/SLO imaging using a low-cost, broadband SLD-based UHR OCT/SLO system. Imaging with UHR OCT/SLO allows for better appreciation of vitreo-retinal pathology and small intraretinal changes, and provides addi-tional information in the outer retina/RPE/choroidal interface during real time acquisition. Two design advantages of the OCT/SLO set-up, the high quality confocal fundus image, and the unique UHR overview provided by the coronal OCT frames, make the UHR OCT/SLO system a valuable addition to clinical fundus imaging.

References 1. Huang D, Swanson EA, Lin CP, et al (1991) Optical coherence

tomography. Science 254: 1178–81 2. Podoleanu AG, Dobre GM, Seeger M, et al (1998) Low coherence

interferometry for en-face imaging of the retina. Lasers and Light 8: 187–92

3. Hee MR, Izatt JA, Swanson EA, et al (1995) Optical coherence tomography of the human retina. Arch Ophthalmol 113: 325–32

4. Schuman JS, Puliafito CA, Fujimoto JG (2004) Optical Coher-ence Tomography of Ocular Diseases (2nd edn). Thorofare (USA): SLACK Inc.

5. Drexler W, Morgner U, Ghanta RK, et al (2001) Ultrahigh-resolution ophthalmic optical coherence tomography. Nature Medicine 7: 502–7

28

6. Drexler W, Sattmann H, Hermann B, et al (2003) Enhanced visu-alization of macular pathology with the use of ultrahigh-resolution optical coherence tomography. Arch Ophthalmol 121: 695–706

7. Nassif N, Cense B, Park BH, et al (2004) In vivo human retinal imag-ing by ultrahigh-speed spectral domain optical coherence tomogra-phy. Opt Lett 29: 480–2

8. Leitgeb RA, Drexler W, Unterhuber A, et al (2004) Ultrahigh resolu-tion Fourier domain optical coherence tomography. Optics Express 12: 2156–65

9. Schmidt-Erfurth U, Leitgeb RA, Michels S, et al (2005) Three-dimensional ultrahigh-resolution optical coherence tomography of macular diseases. Invest Ophthalmol Vis Sci 46: 3393–402

10. Podoleanu AG, Seeger M, Dobre GM, et al (1998) Transversal and longitudinal images from the retina of the living eye using low coherence reflectometry. J Biomed Opt 3: 12–20

11. Podoleanu AG, Dobre GM, Cucu RG, et al (2004) Combined mul-tiplanar optical coherence tomography and confocal scanning oph-thalmoscopy. J Biomed Opt 9: 86–93

12. Hitzenberger CK, Trost P, Lo P, Zhou Q (2003) Three-dimensional imaging of the human retina by high-speed optical coherence tomog-raphy. Opt Express 11: 2753–61

13. Vabre L, Dubois A, Boccara AC (2002) Thermal-light full-field opti-cal coherence tomography. Opt Lett 27: 530–2

14. van Velthoven ME, Verbraak FD, Yannuzzi LA, et al (2006) Imaging the Retina by en-face Optical Coherence Tomography. Retina 26: 129–36

15. Unterhuber A, Povazay B, Bizheva K, et al (2004) Advances in broad bandwidth light sources for ultrahigh resolution optical coher-ence tomography. Phys Med Biol 49: 1235–46

16. Ko TH, Adler DC, Fujimoto JG, et al (2004) Ultrahigh resolution optical coherence tomography imaging with a broadband superlu-minescent diode light source. Optics Express 12: 2112–9

17. American National Standards Institute. American National Stan-dard for Safe Use of Lasers. ANSI , Z 136-I. 2000. New York. Ref Type: Generic

18. Sander B, Larsen M, Thrane L, et al (2005) Enhanced optical coher-ence tomography imaging by multiple scan averaging. Br J Ophthal-mol 89: 207–12

19. Paunescu LA, Ko TH, Duker JS, et al (2006) Idiopathic juxtafoveal retinal telangiectasis: new findings by ultrahigh-resolution optical coherence tomography. Ophthalmology 113: 48–57

20. Ergun E, Hermann B, Wirtitsch M, et al (2005) Assessment of cen-tral visual function in Stargardt‘s disease/fundus flavimaculatus with

ultrahigh-resolution optical coherence tomography. Invest Ophthal-mol Vis Sci 46: 310–6

21. Ko TH, Fujimoto JG, Duker JS, et al (2004) Comparison of ultra-high- and standard-resolution optical coherence tomography for imaging macular hole pathology and repair. Ophthalmology 111: 2033–43

22. Ko TH, Fujimoto JG, Schuman JS, et al (2005) Comparison of ultra-high- and standard-resolution optical coherence tomography for imaging macular pathology. Ophthalmology 112: 1922

23. Wirtitsch MG, Ergun E, Hermann B, et al (2005) Ultrahigh resolu-tion optical coherence tomography in macular dystrophy. Am J Oph-thalmol 140: 976–83

24. Witkin AJ, Duker JS, Ko TH, et al (2005) Ultrahigh resolution opti-cal coherence tomography of birdshot retinochoroidopathy. Br J Ophthalmol 89: 1660–1

25. van Velthoven ME, de Vos K, Verbraak FD, et al (2005) Overlay of conventional angiographic and en-face OCT images enhances their interpretation. BMC Ophthalmol 5: 12

26. van Velthoven ME, Verbraak FD, Garcia PM, et al (2005) Evaluation of central serous retinopathy with en face optical coherence tomog-raphy. Br J Ophthalmol 89: 1483–8

27. Pircher M, Gotzinger E, Leitgeb R, et al (2004) Imaging of polariza-tion properties of human retina in vivo with phase resolved transver-sal PS-OCT. Optics Express 12: 5940–51

28. Paunescu LA, Schuman JS, Price LL, et al (2004) Reproducibility of Nerve Fiber Thickness, Macular Thickness, and Optic Nerve Head Measurements Using StratusOCT. Invest Ophthalmol Vis Sci 45: 1716–24

29. Gurses-Ozden R, Teng C, Vessani R, et al (2004) Macular and Retinal Nerve Fiber Layer Thickness Measurement Reproducibil-ity Using Optical Coherence Tomography (OCT-3). J Glaucoma 13: 238–44

30. Hee MR (2005) Artifacts in optical coherence tomography topo-graphic maps. Am J Ophthalmol 139: 154–5

31. Cucu RG, Podoleanu AG, Rogers JA, Pedro J, Rosen RB (2006) Combined confocal/en face T-scan-based ultrahigh-resolution opti-cal coherence tomography in vivo retinal imaging. Opt Lett 31 (11): 1684–6

Correspondence: Richard B. Rosen, MD, New York Eye and Ear In-firmary, 310 E 14th Street, New York, NY 10003, USA, E-mail: [email protected].