Visualization of Sub-retinal Pigment Epithelium Morphologies of Exudative Macular Diseases by High-Penetration Optical Coherence Tomography

Abstract

purpose. To evaluate the clinical significance of the newly developed long-wavelength probe optical coherence tomography (LP-OCT) for the diagnosis of exudative macular diseases.

methods. Fourteen eyes of 13 participants were prospectively enrolled in the study. There were seven type I and five type II choroidal neovascularization (CNV) cases associated with age-related macular degeneration and idiopathic neovascularization and one case of polypoidal choroidal vasculopathy (PCV). A custom-built LP-OCT based on swept-source OCT (SS-OCT) technology was used. This new OCT uses a probe beam with a wavelength of 1060 nm that provides deeper penetration into the choroid and higher image contrast to the structures beneath the retinal pigment epithelium (RPE) and pathologic tissues than does conventional OCT. The depth resolution is 10.4 μm in tissue and the measurement speed is 28,000 depth scans/s. All the eyes were also examined by standard short wavelength probe OCT (SP-OCT). The image contrasts of the LP- and SP-OCT were qualitatively evaluated and analyzed by Wilcoxon’s paired signed rank test and Spearman’s rank correlation test.

results. In 10 of 14 eyes, high-contrast visualization of the diseases beneath the RPE, CNV, or fibrin was attained. These diseases were almost invisible in the SP-OCT images. The LP-OCT of the remaining eyes also revealed significant improvement in the image contrasts beneath the RPE and CNV. Qualitative evaluation of the image contrasts and subsequent statistical test indicated statistically significant improvement in the image penetration to the choroid of LP-OCT to that of SP-OCT.

conclusions. LP-OCT provided significant improvement in the image contrast of exudative macular diseases.

Age-related macular degeneration (AMD) is the leading cause of social blindness in the United States and Europe. ¹ Exudative macular diseases, including AMD and polypoidal choroidal vasculopathy (PCV), are often related to the development of choroidal neovascularization (CNV) beneath the retinal pigment epithelium (RPE). ^{2 3 4}  

The CNVs in AMD are classified into two pathologic types: type I CNV and type II CNV. ⁵ Type I CNV develops beneath the RPE, whereas type II CNV appears anterior to the RPE. It is known that type I CNV is related to occult CNV appearance in fluorescein angiography (FA) and is often detectable by indocyanine green angiography (ICGA). ⁶ The CNV in PCV also develops under the RPE. Although it appears as a clear point leakage in ICGA, it is not always visible in FA. ⁷  

Conventional optical coherence tomography (OCT) at 830 nm has shown that wavelength provides only a limited ability to visualize structures beneath the RPE. Although OCT occasionally reveals clinically significant structures beneath the RPE, ⁸ the contrast is poor, and it is difficult to distinguish whether they are real structures or imaging artifacts. 

Thus far, ICGA is one of the promising modalities for accessing the diseases under the RPE. However, ICGA is a moderately invasive method, and it has some adverse reactions and results in discomfort of patients. Hence, it is clinically important to establish a new modality that noninvasively reveals the diseases under the RPE. 

The purpose of this study was to demonstrate the performance of the newly developed LP-OCT for the visualization of diseases beneath the RPE and other strongly light-scattering structures. The strategy of LP-OCT for accessing the deep posterior eye is similar to that of ICGA, employs a longer wavelength (near infrared light) than that of FA (visible, yellow-green light). This longer wavelength light is less scattered and absorbed by the retina and choroid, and it provides deeper penetration. 

Based on a similar strategy, our LP-OCT employs a longer wavelength than that of conventional SP-OCT. All the commercially available retinal OCT, including both time-domain OCT and Fourier-domain OCT (FD-OCT), employs the probe beam with a wavelength around 830 nm. The water, the main content of the vitreous, has a local minimum of its absorption at this wavelength. ⁹ This absorption local minimum, called water window, enables the probe beam to access the retina. In contrast to SP-OCT, LP-OCT uses another local minimum of the water absorption at a longer wavelength (i.e., ∼1050 nm). 

It is known that light with a wavelength of ∼1050 nm is less scattered in the choroid and less absorbed in the RPE. Hence, it is suitable for high-penetration imaging of the posterior eye. ^{10 11 12 13 14 15 16} In this study we built LP-OCT that uses a probe light with a center wavelength of 1060 nm along with FD-OCT technology. The FD-OCT scheme provides high-speed volumetric OCT of the posterior eye and the 1060-nm probe light provides high-contrast imaging of the structures beneath the RPE. AMD and PCV patients were examined by this LP-OCT and clinically significant diseases beneath the RPE and other strongly scattering tissues were visualized. 

Materials and Methods

Subjects

In this study, 14 eyes of 13 cases (nine men and four women) were prospectively examined. One of the 14 eyes was rejected because of bad fixation of the eye, and 13 eyes were finally included in the study. The mean age of the subjects was 70.4 ± 14.5 (mean ± SD), and the ages ranged from 37 to 84. The mean age was 71.5 ± 11.0, and the ages ranged from 55 to 84 in the men and was 66.9 ± 25.4 and ranged from 37 to 82 in the women. Seven eyes had type I CNV associated with AMD (five men and two women), one eye had type I CNV associated with idiopathic neovascularization (one woman), four eyes had type II CNV associated with AMD (three men and one woman), and one eye had PCV (one man). The details of the patients involved are summarized in Table 1 . 

Methods

All eyes were examined by using a standard ophthalmoscope, a color fundus camera, FA, ICGA, and SP-OCT (3D OCT1000; Topcon Corp., Tokyo, Japan). The progression of the cataract was examined according to the lens opacities classification system III (LOCS III), ¹⁷ by an experienced ophthalmologist. The decimal fractions of the LOCS III grades were rounded off to the nearest small integer. 

For the SP-OCT examination, the automated depth range adjustment feature based on the mechanical movement of the reference mirror of the 3D OCT-1000 was used. The scanning density was 512 lines per horizontal fast scan and 128 fast scans per vertical slow scan. After these examinations, the subjects were transferred to the optics laboratory of the Computational Optics Group in the University of Tsukuba, where the LP-OCT was built, and examined by LP-OCT according to the volumetric scanning protocol described in the following section. 

The study protocol, purpose of the study, and potential risks of the examination were explained to the patients in oral and written form, and written informed consent was obtained from all the patients. All the examinations conformed to the guidelines in the Declaration of Helsinki, and all the protocols were approved by the institutional review boards of the University of Tsukuba and Tokyo Medical University. 

Long-Wavelength Probe Optical Coherence Tomography

A custom-made LP-OCT was built in the optics laboratory of the Computational Optics Group at the University of Tsukuba (Ibaraki, Japan; Fig. 1 ). This LP-OCT uses a probe beam with a center wavelength of 1060 nm and possesses a depth resolution of 10.4 μm in tissue. The measurement speed is 28,000 depth lines/s which is comparable to that of a commercial FD/spectral domain OCT (SD-OCT). A raster scanning protocol with 512 (horizontal) × 255 (vertical) depth lines corresponding to the 6 × 6 mm² region on the fundus was used for the volumetric scan, where the horizontal scan was the fast scan and the vertical scan was the slow scan. The acquisition speed of the volumetric scan was 4.9 seconds/volume. The sensitivity of this LP-OCT was measured to be 97 dB, which decreases as the signal moves away from the reference delay depth with a decay speed of −5.2 dB/mm. These sensitivity properties provide a rough measure of the depth measurement range of ∼5 mm. The power to the cornea is less than 750 μW, which is safely under the ANSI standard of ∼1.9 mW at this wavelength. ¹⁸  

Our LP-OCT is based on swept-source OCT (SS-OCT) technology, also referred to as optical frequency domain imaging, ¹⁹ which has been applied to the investigation of the posterior eye since 2006. ^{12 13 14} The mathematical and physical principle of this technology is similar to that of SD-OCT, ^{20 21 22 23} and both of the technologies are referred to as FD-OCT. SS-OCT does not employ a broad-band light source which is typical of TD- and SD-OCT, but it employs a high-speed wavelength scanning laser (HSL-1000; Santec, Aichi, Japan). Our SS-OCT uses a high-speed wavelength scanning laser that scans the wavelength of the output beam over the range of 72 nm with a center wavelength of 1060 nm. The scanning frequency of the light source (28 kHz) results in the measurement speed of the SS-OCT of 28,000 depth lines/s. As shown in Figure 2 , the light is coupled into a fiber-based Mach-Zehnder interferometer, and the probe tip of the interferometer is attached to a semicustom fundus scanning head based on the 3D OCT-1000 (Topcon Corp.). The output from the interferometer is detected by a balanced photo detector (BPD), digitized by a personal computer, and processed by custom software, to yield a single depth scan. The signal processing applied by the custom software includes spectral rescaling, digital Fourier transform, despeckle filtering, and logarithmic scale compression. The optical dispersion of the eye was automatically and numerically corrected before the digital Fourier transform. This signal processing procedure is nearly identical with that of standard SD-OCT. The SS-OCT detection scheme, accompanied by transversal raster scanning of the probe, provides a three-dimensional (3-D) OCT volume. In this 3-D measurement mode, the axial motion of the eye between each adjacent horizontal cross-sections was numerically canceled by a correlation-based algorithm. ²⁴ The LP-OCT is described in greater detail in Reference ¹³ . 

In the data reviewing process, the 3-D OCT volume is interactively displayed by a custom OCT viewer (SmartProjection, written in LabView [National Instruments, Austin, TX]; Computational Optics Group, University of Tsukuba). This OCT viewer can apply despeckle filtering based on the overlapping of adjacent cross sections to the horizontal, vertical, and en face directions. The OCT images are displayed with one of the several predefined color maps, including the rainbow scale, gray scale, and inverted gray scale. The signal level at the vitreous is defined as 0 dB, and the OCT image is displayed with a signal range of −10 to +25 dB. This program can also coregister the color fundus photograph, FA, ICGA, and other en face modalities to the 3-D OCT volume and provides a clear comparison between the clinical findings in the OCT and the other modalities. For the quantitative comparison of the OCT images, both of the 3-D OCT data sets acquired by SP-OCT and LP-OCT are displayed by this custom viewer. 

Comparison between LP-OCT and SP-OCT

To determine the high-contrast imaging ability, an observer compared LP-OCT and SP-OCT images of the identical location on the retina. The image contrasts of the clinical features beneath the RPE were qualitatively compared and graded as image contrast enhancement beneath RPE (ICE-RPE). ICE-RPE was graded as positive (+) if the qualitative image contrast improvement was observed with LP-OCT for one or more pathologic features beneath the RPE. ICE-RPE was graded as negative (−) for other cases. 

To evaluate the image penetration into the choroid, we examined the visibility of the choroidal vessels. Horizontal OCT cross-sectional images were qualitatively examined by two retinal specialists (KK and MM) in the following manner: if the bottom arc of the choroidal vessels was visible in more than 50% of the transverse extent of the image, excluding regions with diseases, the choroidal penetration score (CP) was scored as positive (+); otherwise it was scored as negative (−). This examination was conducted for the LP-OCT cross-sections and corresponding SP-OCT images taken at locations identical to those in the LP-OCT images, to compare the choroidal penetration of LP-OCT and SP-OCT. The improvement in the CP of LP-OCT was evaluated against SP-OCT by Wilcoxon’s paired signed rank test. 

The cataract (LOCS III grade) dependency of the penetration-improvement score (PIS) was evaluated by Spearman’s rank correlation. PIS was defined in the following manner based on the CP results: PIS = +1 if the CP of LP-OCT was positive and that of SP-OCT was negative; PIS = −1 if the CP of LP-OCT was negative and the CP of SP-OCT was positive; and PIS = 0 if CPs of LP-OCT and SP-OCT have the same score. 

We also qualitatively reviewed the image contrasts of the sensory retina in the following manner: The image contrasts of the sensory retina in the regions without CNV, fibrin, or any other marked diseases were qualitatively evaluated by two retinal specialists (KK and MM). The improvement in retinal contrast (IRC) was ranked in three grades: positive (+1) for the eyes with contrast improvement in LP-OCT, negative (−1) for the eyes with contrast degradation, and null (0) for the eyes without marked contrast alternation. The correlations between IRC and C/NC LOCS III grades were evaluated by Spearman’s rank correlation. 

Results

The mean logarithmic minimum angle of resolution (logMAR) of the eyes included in the study was 0.67 ± 0.55 (mean ± SD), the logMAR ranged from 1.70 to 0.00 with a median of 0.52, which corresponds to the mean visual acuity of 0.21 ± 0.28 (mean ± SD) and the range from 0.02 to 1.00 with the median of 0.30. 

Type I CNV was diagnosed in 7 (53.8%) of the 13 eyes, and pigment epithelial detachment (PED) was observed in 6 (85.7%) of 7 eyes. Type II CNV was diagnosed in 5 (38.5%) of the 13 eyes, and PED was detected in 2 of 5 eyes. One of the 13 (7.7%) eyes was diagnosed with PCV and showed PED. These diagnoses were based on the clinical findings of the standard examinations including ophthalmoscope, a color fundus camera, FA, ICGA, and SP-OCT. 

The cataract properties of eyes were as follows. Four of the 13 (30.8%) eyes were pseudophakic with intraocular lenses (IOL eyes), 4 (30.8%) showed no marked cortical cataract (C0), and 3 (23.1%) and 2 (15.4%) were graded as C1 and C2. Based on nuclear opalescence, one (7.7%) eye was classified as grade 0 (NO0) and the other eight (61.5%) were classified as NO1. Eight (61.5%) eyes showed no marked posterior subcapsular cataract (P0), whereas one (7.7%) was classified into P2. Based on the nuclear color, one (7.7%) eye showed no marked color (NC0), whereas four (30.8%) were graded as NC1 and 4 (30.8%) as NC2, respectively. 

Contrast Improvement of the Morphologies beneath the RPE

Nine of the 13 (69.2%) eyes showed marked improvement in the qualitative image contrast of the pathologic structures beneath the RPE in the LP-OCT images in comparison to those of the SP-OCT images (ICE-RPE in Table 1 ). These nine eyes included five type I CNV, three type II CNV, and one PCV—namely, 71.4% (5/7) type I CNV, 60.0% (3/5) type II CNV, and 100.0% (1/1) PCV. 

In 5 of the 13 eyes (patients 1-L, 2, 3, 6, and 8), hyperreflective masses beneath the RPE at the PED regions were observed in the LP-OCT images. Although these masses were evident in the LP-OCT images, they were rarely visible in SP-OCT images. 

In patient 3 (PCV), Figures 3c and 3dshow a double-humped PED. In the LP-OCT image, the area beneath the right peak of the PED was filled with a hyperreflective mass with a small circular void region inside, whereas the area beneath the left peak of the PED was relatively hyporeflective. This contrasting appearance of the structures beneath the PED was not evident in the corresponding SP-OCT image, in which the area beneath the PED showed spatially uniform light-scattering. Further, the image penetration of SP-OCT at the thick part of the PED is not sufficient to visualize the structures underneath. The same contrasting appearance is also visible in Figures 3e 3f 3g 3h . By comparing the LP-OCT images with the coregistered ICGA, we found that these hyperreflective masses correspond to the polypoidal leakage of ICGA (arrows 1–4). 

Another type of subpigment epithelial hyperreflective mass was observed in patient 8 (type I CNV). Subpigment epithelial hyperreflective regions were clearly observed in the LP-OCT images (the arrows in Figs. 4f 4h ), whereas they were hardly seen in the SP-OCT images (Figs. 4g 4i) . These regions appeared hypofluorescent both in the early and late phases of FA and ICGA. This observation indicates that the hyperreflectivity was not due to CNV but may have been due to a cluster of fibrin. 

The bottom line of the PED, which may correspond to the Bruch’s membrane is clearly visible in the LP-OCT images (Figs. 4d 4f 4h) , but is not visible in the corresponding SP-OCT images (Figs. 4e 4g 4i) . 

Another sub-RPE structure visualized by LP-OCT is the Bruch’s membrane beneath the CNV. In Figures 3c 3e 3g -i, and 3g-ii, the double-layered appearance of the Bruch’s membrane beneath the CNV was clearly visible, whereas it was hardly visible in SP-OCT images. The Bruch’s membrane beneath the CNV or fibrin was also visible in patients 9 (Fig. 5)and 10. 

Contrast Improvement under CNV and Fibrin

Because of the strong scattering due to CNV and fibrin, it was difficult to visualize the structures through the CNV and fibrin by SP-OCT. In our study, LP-OCT revealed hyperreflective structures under the CNV and/or fibrin (SUCF) in 3 of the 13 type II CNV eyes, which were invisible in the SP-OCT images (SUCF in Table 1 ). 

The examples of this hyperpenetration are shown in Figs. 6d 6e 6f 6g 6h . LP-OCT images (Figs. 6d 6f 6h)revealed the RPE beneath the CNV, whereas SP-OCT images (Figs. 6e 6g 6i)did not provide significant contrast. Figure 6hshows partial disappearance of the RPE beneath the CNV. A comparison of this image with the coregistered late-phase FA image indicates that this region of RPE defect corresponded to the active hyperfluorescent region. In Figure 6d -i, relatively large clusters of CNV were visualized (Fig. 6d -ii, yellow curves); however, they are hardly visible in the corresponding SP-OCT image (Fig. 6e) . 

Figures 5h and 5ialso show the difference in contrast beneath the CNV between LP-OCT and SP-OCT. In the LP-OCT image, a line connected to the RPE under the CNV, which may correspond to Bruch’s membrane, was visible (arrows), whereas this structure was hardly visible in the corresponding SP-OCT. 

In Patient 5, thick fibrin/CNV existed above the PED. Hyperreflective fragments were visible under the fibrin/CNV (Fig. 7f -ii, arrows), which may indicate a fragmented RPE, which is not visible in the corresponding SP-OCT image (Fig. 7g) . This segmented RPE appeared as a C-shaped hyperreflective region in an en face LP-OCT cross-section (Fig. 7d , white arrow) with high contrast. Although the corresponding SP-OCT image (Fig. 7e)shows a similar structure, the contrast is poor and the boundary between this RPE and fibrin/CNV was not visualized with sufficient contrast. Another horizontal LP-OCT cross-section (Fig. 7h)shows the defect of the RPE which corresponds to the opening of the C-shaped structure in Figure 7d . According to these morphologies, it is reasonable to hypothesize that the development route of the CNV is that indicated by the red arrows in Figures 7d and 7h . 

Visualization of the Choroid

The low-scattering and low-absorption properties of LP-OCT results in a higher image penetration into the choroid compared with the penetration of SP-OCT. In 92.3% (12/13; both MM and KK) of eyes, the CP of LP-OCT was positive, whereas it was positive in only 23.1% (3/13, KK) and 7.7% (1/13, MM) of eyes with SP-OCT (CP of Table 1 ). An improvement of penetration was observed in 69.2% (9/13, KK) and 84.6% (11/13, MM) eyes with LP-OCT. Wilcoxon’s paired signed rank test indicates a statistically significant improvement of the choroidal penetration with LP-OCT: P = 0.0060 for KK and P = 0.0011 for MM. 

The LOCS III NC-grade dependency of PIS was found as follows: 100.0% (1/1, for both KK and MM) of the NC0 eyes, 75.0% (3/4, KK and MM) of the NC1 eyes, 100.0% (4/4, KK and MM) of the NC2 eyes, and 50.0% (2/4, KK) and 75.0% (3/4, MM) of the IOL eyes showed improved penetration into the choroid. Although the statistical significances were poor (P = 0.073), Spearman’s rank correlation results suggest a moderate positive correlation (ρ = 0.62, KK). The result of the examination by MM indicate no statistical significance (P = 0.56, ρ = 0.23). The averaged PISs for each NC score are shown in Figure 8a , where all the penetration scores including that of KK and MM are averaged for each LOCS III grade. 

The LOCS III C-grade dependency of PIS was found as follows: 50.0% (2/4, KK) and 75.0% (3/4, MM) C0 eyes, 100.0% (3/3, KK and MM) C1 eyes, and 100.0% (2/2, KK and MM) C2 eyes showed improved penetration to the choroid. Although no statistical significance was found (P = 0.12 for KK and P = 0.33 for MM), Spearman’s rank correlation test suggested moderate positive correlations (ρ = 0.55 for KK and ρ = 0.37 for MM) between C-grade and PIS. Figure 8bshows the average PISs for each C score. 

The nuclear opalescence grade (NO) and posterior subcapsular cataract grade (P) of LOCS III were not used in this study because the distributions of these two parameters were strongly uneven in the patients (Table 1) . 

Image Contrast of the Retina

Contrast improvement in the part of the sensory retina is summarized as follows: five (38.5%, KK) and 4 (30.8%, MM) of 13 eyes demonstrated a positive improvement in IRC, whereas 7 (53.8%, KK) and 9 (69.2%, MM) eyes showed null improvement. Negative improvement was observed in one (7.7%, KK) and no (MM) eyes. The results are summarized in Tables 1 and 2 . 

The cataract dependency of IRC was determined as follows: 25.0% (1/4, KK) and 0 (MM) C0 eyes, 33.3% (1/3, KK and MM) C1 eyes, and 50.0% (1/2, KK and MM) C2 eyes showed positive improvement in retinal contrast (Table 1) . Although Spearman’s rank correlation test did not show a statistically significant correlation between IRC and LOCS III C-grade (P = 0.42 for KK and P = 0.17 for MM), fair (ρ = 0.31 for KK) and moderate (ρ = 0.50 for MM) positive correlations are suggested. The average scores of all 2 graders are summarized as a function of C-grade in Figure 9b . 

Positive IRC was observed in 100.0% (1/1, KK and MM) NC0 eyes, 50.0% (2/4, KK), and 25.0% (1/4, MM) NC1 eyes, and 25.0% (1/4, KK and MM) NC2 eyes. However Spearman’s rank correlation test showed no statistical significance (P = 0.90 for KK and P = 0.77 for MM). The average scores of the two graders are summarized as a function of NC-grade in Figure 9a . 

An appealing visualization in the sensory retinal region was observed in patient 9 (Fig. 5) . Webbing structures, which may be a network of fibrin, are visible in the region of retinal detachment (RD) in the LP-OCT image (Fig. 5f) , whereas SP-OCT provides a limited contrast (Fig. 5g) . This difference in image contrast is also evident in the en face OCT slices (Figs. 5d 5e) . The webbing structure is clearly visualized in the LP-OCT image (arrows), whereas it is nearly invisible in the corresponding SP-OCT slice. 

Discussion

It is generally known that the image contrast of the structures beneath the RPE is poor with SP-OCT because of the high optical absorption of the RPE at a wavelength of 830 nm ²⁵ and the light-scattering and absorption properties of the sub-RPE tissue. On the other hand, the optical absorption of the RPE at a wavelength of 1060 nm, the probe wavelength of LP-OCT, is one tenth of that at 830 nm. ²⁵ It is reasonable to hypothesize that LP-OCT provides a higher image contrast of the morphologies beneath the RPE than SP-OCT does. In this study a marked improvement in image contrast beneath the RPE was observed in 69.2% eyes. This result supports our hypothesis. 

PCV is characterized by polypoidal leakages detected by ICGA, but not always seen in FA. ^{2 3 4 7} Although this polypoidal leakage indicates sub-RPE development of polypoidal CNV, it has been difficult to visualize this CNV in vivo by SP-OCT. ^{26 27} In our study, sub-PED hyperscattering masses were visualized in a PCV eye (Figs. 3c 3e 3g -i, 3g-ii). According to a coregistered ICGA image (Fig. 3k) , it has been shown that the positions of the masses correspond to the position of the polypoidal leakage. This suggests that LP-OCT enabled noninvasive visualization of the sub-PED CNV in vivo. This hyperpenetration of the sub-PED structure can also be attributed to the optical absorption properties of the RPE. 

Besides this low absorption of the RPE at 1060 nm, the low scattering property of longer wavelength light may contribute to the improvement in image contrast. In general, it is difficult to visualize the structures beneath the hyperreflective masses (e.g., CNV or fibrin), because the probe light of OCT is highly scattered by these tissues and cannot penetrate them. Despite this high scattering by the tissue, it is known that long-wavelength light is less scattered than short-wavelength light. ²⁸ In our study, the structures beneath the CNV and/or fibrin, which were not visualized by SP-OCT, were visualized in three eyes. This may be attributed to the general light-scattering property, because the scattering coefficients of CNV and fibrin may decrease as the wavelength increases. 

It has been theoretically indicated that the scattering coefficient of the sensory retina is nearly identical at 830 nm (SP-OCT) and 1060 nm (LP-OCT), ^{11 13} which indicates that the image contrast of the sensory retina may be similar in the SP- and LP-OCT images, if cataract does not exist. Only a preliminary study has been conducted to examine this issue (Chen Y, et al. IOVS 2008;49:ARVO E-Abstract 931), and the detailed investigation will be an important future study. 

The wavelength dependency of the light scattering also suggests that LP-OCT may provide a higher contrast to sensory retina in the cataract eyes because the amount of probe light scattered by the cataract is less in LP-OCT. Recently, Považay et al. qualitatively showed that LP-OCT produced a higher image contrast in eyes with cataract than SP-OCT did. ¹⁵ Our results showing cataract dependency of the OCT contrast do not contradict the findings in that study. 

Although the measured sensitivity of LP-OCT and the officially announced sensitivity of SP-OCT (3D OCT-1000; Topcon) are nearly identical, some pairs of OCT images show the difference in their signal strengths. The wavelength dependency of the cataract may be a reason for this difference. We also suspect that this is due to the spatial localization of the cataract (i.e., the difference in the path of the probe beam and its resulting difference of the amount of vignetting by the cataract may alter the signal strengths). Furthermore, the difference in the measurement condition may also alter the signal strength. The SP-OCT measurement was performed by a clinical expert with the semiautomatic alignment function of this particular OCT equipment, whereas the LP-OCT measurements were performed by an engineering expert after a manual alignment process. 

One last issue that has to be mentioned is the effect of multiple scattering in the choroid as a potential limiting factor of LP-OCT. We ignored this effect in this study. We thought ignoring multiple scattering to be reasonable, because, in OCT imaging, only ballistic and semiballistic photons contribute to the image formation. ^{29 30} This is due to the high confocality and narrow coherence gate of the OCT imaging. On the other hand, a recent study using polarization sensitive OCT shows a polarization scrambling appearance at the RPE. Although the origin of this effect is still not clear, it is suspected that this appearance is associated with multiple scattering. ³¹ The future study of multiple scattering will provide more clear and accurate understanding of LP-OCT images. 

Conclusions

We demonstrated the application of a newly developed LP-OCT, to investigate exudative macular diseases, including AMD and PCV, in 13 eyes of 14 patients. Based on the qualitative comparison between LP-OCT and SP-OCT, it was shown that LP-OCT has a higher image penetration than SP-OCT for the structures beneath the PED, CNV, and fibrin. The higher penetration of LP-OCT in the choroid in comparison to that of SP-OCT was confirmed with statistical significance. The cataract dependence of the improvement in the penetration of LP-OCT compared with SP-OCT was examined. Although no statistical significance was found, our results did not contradict the physically theoretical prediction and previous qualitative demonstration: the image quality gain in LP-OCT compared with that in SP-OCT in cases of more severe cataract. 

 Supported by the Japan Society for the Promotion of Science (JSPS) through the contracts of KAKENHI 04210026 and 18.3827; the Japan Science and Technology Agency (JST) through the contract of Development of Systems and Technology for Advanced Measurement and Analysis; and the Special Research Project of Nanoscience at the University of Tsukuba. Shuichi Makita is supported by the postdoctoral fellow program of JSPS.

 Submitted for publication May 9, 2008; revised June 20 and July 22, 2008; accepted October 10, 2008.

 Disclosure: Y. Yasuno, Topcon Corp. (C), Tomey Corp. (C), Nidek (C); M. Miura, None; K. Kawana, None; S. Makita, None; M. Sato, None; F. Okamoto, None; M. Yamanari, None; T. Iwasaki, None; T. Yatagai, None; T. Oshika, None

 The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked “advertisement” in accordance with 18 U.S.C. §1734 solely to indicate this fact.

 

Table 1.

 

Patients and Their Characteristics

Patient ID	Eye	Sex	Age	logMAR	VA	Diagnosis	CNV Type	PED	LOCS III							ICE-RPE	SUCF	CP in LP (KK)	CP in SP (KK)	PIS (KK)	CP in LP (MM)	CP in SP (MM)	PIS (MM)	IRC (KK)	IRC (MM)
																												C	NO	P	NC
1	R	F	80	0.22	0.6	AMD	I	+	IOL	IOL	IOL	IOL	+	−	+	−	+1	+	−	+1	+	+
	L	F	80	1.70	0.02	AMD	I	−	IOL	IOL	IOL	IOL	+	−	+	+	0	+	−	+1	+	+
2	R	M	78	0.30	0.5	AMD	I	+	2	1	0	2	+	−	+	−	+1	+	−	+1	+	+
3	R	M	55	0.70	0.2	PCV		+	1	1	0	2	+	−	+	−	+1	+	−	+1	0	0
4	L	M	84	0.52	0.3	AMD	I	+	1	1	0	1	−	−	+	−	+1	+	−	+1	+	+
5	L	M	57	0.10	0.8	AMD	II	+	0	1	0	1	+	+	+	−	+1	+	−	+1	−	0
6	R	M	82	0.40	0.4	AMD	I	+	2	1	2	2	+	−	+	−	+1	+	−	+1	0	0
8	R	M	76	1.53	0.03	AMD	I	+	1	1	0	2	+	−	+	−	+1	+	−	+1	0	0
9	L	M	70	1.10	0.08	AMD	II	−	0	1	0	1	+	−	+	−	+1	+	−	+1	+	0
10	R	M	59	0.70	0.2	AMD	I	+	0	1	0	1	−	−	−	−	0	−	−	0	0	0
11	L	F	82	1.22	0.06	AMD	II	−	IOL	IOL	IOL	IOL	−	+	+	−	+1	+	−	+1	0	0
12	L	M	76	0.00	1	AMD	II	−	IOL	IOL	IOL	IOL	−	−	+	+	0	+	+	0	0	0
13	L	F	37	0.22	0.6	IN	II	+	0	0	0	0	+	+	+	+	0	+	−	+1	0	0

 KK and MM represent the two graders. Patient 7 was excluded from the study because of bad fixation of the eye. VA, visual acuity; IN, idiopathic neovascularization; PED, pigment epithelial detachment; LOCS III, lens opacities classification system III; C, cortical cataract; NO, nuclear opalescence; P, posterior subcapsular cataract; NC, nuclear color; IOL, intraocular lenses; ICE-RPE, the score for image contrast enhancement beneath RPE; SUCF, structures under the CNV and/or fibrin; CP, choroidal penetration score; LP, high penetration OCT; SP, standard penetration OCT; PIS, penetration improvement score; IRC (improvement in retinal contrast), the score for the contrast enhancement of the sensory retina.

Figure 1.

 

The custom-built LP-OCT. On the right is a high-speed wavelength scanning light source and an OCT engine consisting of a fiber-based Mach-Zehnder interferometer. This interferometer is attached to a semicustom fundus scanning-head based on the 3D OCT-1000 (Topcon Corp.). The corrected optical signal is transferred to a personal computer and processed by custom software to yield an OCT image. Inset: an example of volumetric visualization of a retina of an eye with age-related macular degeneration (type II CNV) measured by LP-OCT.

Figure 2.

 

Schematic of LP-OCT. HSL, high-speed wavelength scanning laser; C, optical circulator; PC, polarization controller; and BPD, balanced photo-detector. This optical setup is based on a fiber Mach-Zehnder interferometer.

Figure 3.

 

Patient 3: a 55-year-old man who presented with visual disturbance in his right eye for 3 years. Based on the ophthalmoscopic, FA, ICGA, and OCT examinations, PCV was diagnosed. He was treated by photodynamic therapy 1 month before the OCT examination. (a) Color fundus photograph and (b) FA. (c), (e), and (g) are the LP-OCT images and (d), (f), and (h) are the corresponding SP-OCT images. (g-ii) and (h-ii) are respectively identical with (g-i) and (h-i) except for the color map used. (i) En face projection of the OCT (the depth oriented average of the logarithmic OCT image), (j) and (k) are parts of the FA and ICGA images which are coregistered to the measurement area of LP-OCT. (a, b, i–k) Yellow lines: the scanning positions of OCT.

Figure 4.

 

Patient 8: a 76-year-old man who presented with visual disturbance in his right eye for 10 years. Based on the ophthalmoscopic, FA, ICGA, and OCT examinations, AMD was diagnosed, along with type I CNV. (a) Color fundus photograph, (b) FA, and (c) ICGA. (d, f, h) The LP-OCT images (horizontal cross-sections); (e, g, i) the corresponding SP-OCT images. (a–c) Yellow lines: the scanning positions of OCT.

Figure 5.

 

Patient 9: a 70-year-old man who presented with visual disturbance in his left eye for 8 months. Based on the ophthalmoscopic, FA, ICGA, and OCT examinations, AMD was diagnosed, along with type II CNV. Three months before the LP-OCT examination, the eye was treated with photodynamic therapy. (a) Color fundus photograph and (b) early- and (c) late-phase FA. (d, e) The en face cross sections by LP-OCT and SP-OCT; (f, h) the horizontal cross-sections of LP-OCT; and (g, i) the corresponding SP-OCT images. (j) ICGA image. (a–c, j) Yellow lines: the scanning positions of OCT.

Figure 6.

 

Patient 11: an 82-year-old woman who presented with visual disturbance in her left eye for a week. Based on the ophthalmoscopic, FA, ICGA, and OCT examinations, AMD was diagnosed, along with type II CNV. (a) Color fundus photograph and (b) FA in the early and (c) late phases registered with LP-OCT volume. (d-i, d-ii, f, h) Horizontal LP-OCT cross sections; (e, g, i) the corresponding SP-OCT images. (d-i, d-ii) Images are identical except the yellow curves in (d-ii), which indicate the clusters of CNV. (a–c) Yellow lines and (c) horizontal lines with arrowheads: scanning positions of OCT.

Figure 7.

 

Patient 5: a 57-year-old man who presented with visual disturbance in his left eye for 18 months. Based on the ophthalmoscopic, FA, ICGA, and OCT examinations, AMD was diagnosed, along with type II CNV. (a) Color fundus photograph and FA in the (b) early-, and the (c) late phase. (d, e) En face cross-sections extracted from the LP-OCT volume and the SP-OCT volume, respectively. (f-i, f-ii, h) Horizontal LP-OCT cross sections and (g) are an SP-OCT image. (f-i, f-ii) Images are identical except for the color mapping. (a–c) Yellow lines: scanning positions of OCT. (h) Horizontal yellow arrows: the depth position on which (d) was extracted.

Figure 8.

 

The NC (a) and C (b) dependencies of the averaged penetration score.

Table 2.

 

Contrast Improvement Score of the Retina

Observer	Positive	Null	Negative
KK	38.5 (5)	53.8 (7)	7.7 (1)
MM	30.8 (4)	69.2 (9)	0.0 (0)
Average	34.6	61.2	3.8

 KK and MM represent the graders. Each cell represents the percentage of the 13 eyes (number of eyes). The positive score indicates the contrast improvement in the sensory retina, whereas the negative score indicates the contrast degradation. The null score indicates no significant difference in the image contrast.

Figure 9.

 

The NC (a) and C (b) dependencies of the improvement score of the contrast of the sensory retinal (IRC).