Masayuki Nukada

Three-dimensional imaging of lamina cribrosa defects in glaucoma using swept-source optical coherence tomography.

PURPOSE To visualize lamina cribrosa defects using three-dimensional (3D) swept-source optical coherence tomography (SS-OCT), and to determine the factors associated with this feature. METHODS All subjects were examined using an SS-OCT prototype system, which uses a tunable laser as a light source, operated at 100,000 Hz A-scan repetition rate in the 1050-nm wavelength. A 3D raster scan protocol consisting of 256×256 A-scans was acquired over a square area of 3 mm×3 mm centered on the optic disc. En face sectioned volume and serial en face images and orthogonal (horizontal and vertical) serial B-scans were evaluated. RESULTS A total of 182 eyes of 111 patients with glaucoma and 29 healthy eyes of 26 subjects were included. Twenty full-thickness focal lamina cribrosa defects were found in 12 (6.6%) of 182 eyes with glaucoma, whereas no lamina defects were found in healthy eyes. Nine eyes (75.0%) showed 15 full-thickness lamina cribrosa defects near the margin of the lamina cribrosa, and 3 eyes showed 4 lamina defects at the margin, as if detached from the sclera. Focal lamina cribrosa defects corresponded with neuroretinal rim thinning, concurrent or previous disc hemorrhages, abnormal circumpapillary retinal nerve fiber layer thickness, and visual field defects. The presence of lamina cribrosa defects was significantly associated with longer axial length and disc hemorrhages (P=0.033 and 0.024, respectively). CONCLUSIONS 3D SS-OCT imaging allows visualization of the lamina cribrosa defects, which may be more prevalent in eyes with longer axial length and related to disc hemorrhages.

Macular Ganglion Cell Layer Imaging in Preperimetric Glaucoma with Speckle Noise–Reduced Spectral Domain Optical Coherence Tomography

OBJECTIVE To visualize the macular ganglion cell layer (GCL) and measure its thickness in normal eyes and eyes with preperimetric glaucoma, using speckle noise-reduced spectral domain optical coherence tomography (SD-OCT). DESIGN Retrospective consecutive case series. PARTICIPANTS Thirty-seven eyes of 37 patients with preperimetric glaucoma and 39 normal eyes of 39 volunteers. METHODS Vertical and horizontal SD-OCT B-scan images were acquired with minimal speckle noise by using eye-tracking to obtain and average 50 B-scans at each identical location of interest. B-scan images were manually analyzed for GCL, retinal nerve fiber layer (RNFL), and inner plexiform layer shapes and thicknesses in the macula. MAIN OUTCOME MEASURES Macular GCL images and thickness in normal eyes and in eyes with preperimetric glaucoma. RESULTS The macular GCL was clearly seen on speckle noise-reduced SD-OCT images in normal eyes and eyes with preperimetric glaucoma. In each eye with preperimetric glaucoma, thinning of the macular GCL was visually apparent, particularly on vertical scans. The mean regional macular GCL was most severely thinned in the inferior perifoveal region, where its thickness was <70% of its normal thickness in 30 (81.1%) of the 37 eyes and <50% of its normal thickness in 13 (35.1%) of the 37 eyes. When the sensitivity and specificity for detecting abnormal thinning (outside the lower limit of 99% confidence interval [CI] for the means in the 39 normal eyes) in at least one 0.5-mm segment or sector were compared, the macular GCL on vertical B-scans exhibited higher sensitivity (81.1%) than the other layers on vertical B-scans (99% CI, 5.4%-59.5%; P = 0.00075-0.02100), the macular GCL (99% CI, 40.5%; P = 0.00027) on horizontal B-scans, the other layers (99% CI, 5.4%-48.6%; P<0.00048-0.00400) on horizontal B-scans, and circumpapillary RNFL automatically measured on SD-OCT (54.1%; P = 0.021), and scanning laser polarimetry with variable corneal compensation (24.3%; P = 0.00095). All the macular layers on both the vertical and horizontal B-scans and circumpapillary RNFL thickness exhibited comparable specificity (91.4-100.0%, statistically not different). CONCLUSIONS Speckle noise-reduced SD-OCT imaging allowed clear visualization and measurement of the macular GCL, which was severely thinned in eyes with preperimetric glaucoma. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Detection of localized retinal nerve fiber layer defects in glaucoma using enhanced spectral-domain optical coherence tomography.

OBJECTIVE To compare retinal nerve fiber layer (RNFL) defects on fundus photographs with circumpapillary RNFL (cpRNFL) thinning or disruption on images obtained by speckle-noise-reduced spectral-domain optical coherence tomography (enhanced SD OCT), single-scan SD OCT, and single-scan time-domain OCT (TD OCT). DESIGN Retrospective, comparative case series. PARTICIPANTS Forty-four eyes of 44 patients with open-angle glaucoma with localized, wedge-shaped RNFL defects on red-free photographs and 35 normal eyes of 35 volunteers. METHODS Cross-sectional images of the cpRNFL and cpRNFL thinning, compared with the confidence interval limit of the normative database where the RNFL defect was photographically identified, were compared between the 3 types of OCT instruments: enhanced SD OCT (SD OCT with eye tracking and averaging of 16 images at the same location to reduce speckle noise; Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany), single-scan SD OCT (RTVue-100; Optovue, Fremont, CA), and single-scan TD OCT (Stratus; Carl Zeiss-Meditec, Dublin, CA). MAIN OUTCOME MEASURES Cross-sectional images of localized RNFL defects on red-free fundus photographs, sensitivity for detecting the photographic RNFL defect, and sensitivity and specificity for detecting glaucoma as having at least 1 abnormally thinned sector on the cpRNFL thickness map on OCT. RESULTS Among the 44 eyes with glaucoma, 65 RNFL defects were identified on red-free fundus photographs. The cpRNFL boundaries were clearer on enhanced SD OCT images than on single-scan SD OCT or TD OCT images, particularly in regions corresponding to the RNFL defects. Enhanced SD OCT revealed various degrees of cpRNFL thinning, and disruption of cpRNFL reflectivity was seen in the same location as the photographic RNFL defect for 23 (35.4%) of the 65 RNFL defects. The RNFL defects were significantly less likely to be detected by single-scan TD OCT or SD OCT (P = 0.002 and P = 0.006, respectively) when the RNFL was not disrupted. Enhanced SD OCT was more sensitive in detecting the RNFL defects that were not disrupted compared with single-scan TD OCT (P<0.0001) or SD OCT (P<0.0001). Enhanced SD OCT had better sensitivity and specificity for detecting glaucoma compared with single-scan TD OCT or SD OCT (sensitivity, P = 0.006 and P = 0.001; specificity, P = 0.001 and P = 0.004, respectively). CONCLUSIONS These results suggest that speckle-noise reduction can improve the detection of photographic RNFL defects in which cpRNFL reflectivity on OCT images is not disrupted. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Three-dimensional imaging of the macular retinal nerve fiber layer in glaucoma with spectral-domain optical coherence tomography.

PURPOSE To investigate the three-dimensional (3D), spectral-domain (SD) optical coherence tomography (3D,SD-OCT) imaging of the macular retinal nerve fiber layer (RNFL) in eyes with glaucoma. METHODS The study included 38 eyes of 38 patients with glaucoma and 38 normal eyes of 38 volunteers. With a 3D raster scan SD-OCT protocol, 512 × 128 axial scans were acquired over a 6-mm(2) area of the macula. Findings on 3D,SD-OCT images were compared with those on color and red-free fundus photographs and time-domain (TD) OCT. RESULTS Fourteen (30.4%) more RNFL defects were detected on 3D,SD-OCT images than on color fundus photographs. Of these 14, 12 were detected in 10 (90.9%) of 11 eyes with tessellated fundi (P < 0.0001). On 3D,SD-OCT images, complete loss of the RNFL reflectivity was seen in 63.0% of the RNFL defects and thinning of the RNFL in the rest. On TD-OCT cpRNFL analysis, RNFL defects that appeared on 3D,SD-OCT as a complete loss of RNFL reflectivity were detected more often (P = 0.012) than those that appeared as thinning of the RNFL. Inter-rater agreement was better for RNFL defects on 3D,SD-OCT (0.85) than for those on color (0.62-0.64) or red-free (0.68-0.70) fundus photographs. However, 3D,SD-OCT macular RNFL thickness measurements were substantially reproducible but not as reproducible as macular retinal thickness measurements, and neither was as sensitive as TD-OCT cpRNFL thickness measurements for detecting glaucoma. CONCLUSIONS 3D,SD-OCT imaging of the macular RNFL is an effective means of detecting macular RNFL defects and their severity in eyes with glaucoma.

Wide 3-dimensional macular ganglion cell complex imaging with spectral-domain optical coherence tomography in glaucoma.

PURPOSE To determine whether measurement of ganglion cell complex (GCC) thickness over a wide area (8-mm diameter) can improve the glaucoma-discriminating ability of spectral-domain optical coherence tomography (SD-OCT) compared to that in the standard macular area (6-mm diameter). METHODS Ninety-three subjects were enrolled, including 46 healthy eyes of 46 volunteers and 47 eyes of 47 glaucoma patients (23 eyes with preperimetric glaucoma [PPG] and 24 eyes with early glaucoma [EG]). All patients underwent SD-OCT raster scanning over a 9 mm × 9 mm square area centered on the fovea. Areas under the receiver operating characteristic curves (AROCs) were compared between wide sector (1-8-mm ring) and standard-size sector (1-6-mm ring) charts. RESULTS AROCs for average GCC thickness in the wide chart were significantly greater than those of the standard chart in eyes with PPG (0.928 vs. 0.891; P = 0.038), EG (0.912 vs. 0.861; P = 0.003), and both (0.920 vs. 0.876; P = 0.004). Overall, the AROCs of regional GCC thicknesses were nearly comparable between the middle ring (4-6 mm) and outer ring (6-8 mm). Coefficients of variation were 0.68% and 0.97% in the standard and wide sector charts, respectively, in eyes with PPG, and 0.45% and 0.72% in the standard and wide sector charts, respectively, in eyes with EG. CONCLUSIONS Addition of the GCC thickness outside the macula to the standard macular GCC thickness significantly increased the glaucoma-discriminating ability of SD-OCT.

Frequency-doubling technology and retinal measurements with spectral-domain optical coherence tomography in preperimetric glaucoma.

BackgroundTo determine the relationship between visual fields and retinal structures measured with spectral-domain optical coherence tomography in preperimetric glaucoma (PPG).MethodsTwenty-six eyes of 26 patients with PPG and 20 healthy eyes of 20 volunteers were included. All patients underwent Heidelberg retina tomography-2 (HRT2), standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and RTVue-100. SAP and FDT indices, HRT parameters, and circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (mGCC) thicknesses were correlated using Pearson’s test. Areas under the receiver operating characteristic curves (AUROCs) and sensitivity/specificity based on each parameter’s definition of abnormalities were compared between parameters.ResultsSignificant differences were found in FDT-MD, FDT-PSD, SAP-PSD, cpRNFL, and mGCC parameters (p < 0.001–0.015), but not in SAP-MD or HRT parameters, between PPG and control groups. Significant correlations were not found between visual field indices and structural parameters, except between FDT-MD and HRT rim area (r = 0.450, p = 0.021) and between FDT-PSD and temporal cpRNFL thickness (r = 0.402, p = 0.021). AUROCs for cpRNFL (p = 0.0047–0.033) and mGCC (p = 0.0082–0.049) parameters were significantly better than those of HRT parameters, whereas significant differences were not found between FDT indices and cpRNFL or mGCC parameters or between cpRNFL and mGCC parameters. Adding average cpRNFL or mGCC thickness to FDT-MD significantly increased sensitivity compared to single parameters (p = 0.016–0.031).ConclusionsStructural and functional parameters were poorly correlated but complementary for glaucoma detection in PPG. Combining these parameters may improve PPG diagnosis.

Biometric Features of Peripapillary Atrophy Beta in Eyes with High Myopia

PURPOSE To evaluate peripapillary atrophy β (PPA-β) characteristics in highly myopic eyes, using simultaneous confocal scanning laser ophthalmoscopy (cSLO) and enhanced spectral-domain optical coherence tomography (SD-OCT). METHODS The authors retrospectively analyzed 61 highly myopic (≥ -6.0 D) eyes without myopic retinopathy. cSLO fundus images were used to measure the distances from the foveal center to the temporal and nasal margins of the PPA-β zone; horizontal cross-sectional SD-OCT images, to determine the position where the inner plexiform layer (IPL) terminates within the PPA-β zone; and A-mode ultrasonography, to measure axial length. RESULTS The distance from the foveal center to the PPA-β zone temporal margin (2.68-4.39 mm) correlated with the circumferential extent of PPA-β (P <0.001, r = -0.49). The distance from the foveal center to the nasal margin (3.41-5.60 mm) correlated with the ovality index of the optic disc (P <0.001, r = -0.51) and with the axial length (P <0.05, r = 0.26). PPA-β zone width (0.20-2.05 mm) correlated with the circumferential extent of PPA-β (P <0.001, r = 0.42), ovality index of the optic disc (P <0.001, r = -0.68), and axial length (P <0.05, r = 0.32). The IPL termination within the PPA-β zone was significantly closer to the optic disc when the circumferential extent of PPA-β was large (P <0.01, r = 0.36). CONCLUSIONS Interindividual variations in biometric features of PPA-β in highly myopic eyes showed different associations with axial length, degree of disc ovality, and circumferential extent of PPA-β.

Imaging of localized retinal nerve fiber layer defects in preperimetric glaucoma using spectral-domain optical coherence tomography.

Purpose:To characterize preperimetric retinal nerve fiber layer (RNFL) defects on speckle noise–reduced spectral-domain optical coherence tomography (SD-OCT), and to determine whether detection of preperimetric RNFL defects can be improved by speckle noise reduction. Patients and Methods:Thirty-two eyes of 32 patients with preperimetric glaucoma and 30 normal eyes of 30 volunteers underwent complete ophthalmic examinations and scanning by speckle noise–reduced SD-OCT (Spectralis), single-scan SD-OCT (RTVue-100), and single-scan time-domain (Stratus) OCT. Results:All 40 RNFL defects identified by photography had angular widths <30 degrees and no disruption of RNFL reflectivity on Spectralis. Circumpapillary RNFL (cpRNFL) boundaries were accurately determined by Spectralis for 38 (95.0%) of the 40 defects, by RTVue-100 for 25 (62.5%), and by Stratus OCT for 23 (57.5%). Sensitivity for the detection of RNFL defects (cpRNFL thinning to <1% of normal for an age-matched database) was 15% for Stratus, 42.5% for RTVue, and 47.5% for Spectralis on sector maps and significantly higher for SD-OCT on temporal-superior-nasal-inferior-temporal (TSNIT) thickness graphs: RTVue-100 (57.5%; P=0.031) and Spectralis (90.0%; P=0.0001). On the basis of TSNIT thickness graphs, sensitivity for the detection of RNFL defects was significantly higher for Spectralis compared with RTVue-100 (P=0.001) and Stratus (P=0.0005). Spectralis TSNIT graphs were more sensitive (P=0.001) for glaucoma detection without significant reduction (P=0.125) in specificity compared with Spectralis sector maps. Conclusions:Our results suggest that accurate measurement of cpRNFL thickness by speckle noise–reduced SD-OCT and a comparison of the results with normative database using TSNIT graphs are required to improve the sensitivity for detecting preperimetric RNFL defects.

Time-lapse imaging of retinal angiogenesis reveals decreased development and progression of neovascular sprouting by anecortave desacetate.

PURPOSE To elucidate the effects of anecortave desacetate (AD) treatment on the kinetics of neovascular sprouting and its molecular mechanisms in retinal explants and during retinal vascular development in mice. METHODS The antiangiogenic effects of AD on retinal angiogenesis were evaluated using two different models: a retinal explant model treated with vascular endothelial growth factor (VEGF) and a mouse model of postnatal retinal vascular development. Time-sequential observation was followed by the quantification of movements in neovascular sprouts and microglia. Real time-PCR was performed for the measurement of mRNA levels. RESULTS AD treatment significantly reduced the number of neovascular sprouts in retinal explants in a dose-dependent manner. Time-lapse imaging demonstrated that AD suppressed the new development and elongation of neovascular sprouts and the motility of tip cells. Moreover, AD treatment disturbed the filopodial extension and significantly decreased the transcriptional levels of KDR and platelet-derived growth factor-B, which are highly expressed in tip cells. In addition, it was confirmed that AD inhibited postnatal development of the retinal vasculature in mice, including filopodial extension in tip cells. These data suggest that AD suppresses both the development and the progression of sprouting angiogenesis. Interestingly, VEGF-induced microglial movements were also reduced in the retinal explants treated with AD. These changes were consistent with decreased mRNA levels of SDF-1 and Flt-1, which regulate the activation of inflammatory cells. CONCLUSIONS AD inhibited both the development and the progression of VEGF-induced retinal angiogenesis mediated, in part, by the suppression of tip cell motility in two angiogenic models.