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Purpose: Swept-source (SS) OCT angiography (OCTA) was used to determine the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with nonexudative age-related macular degeneration (AMD)., Design: Prospective, observational, consecutive case series., Participants: Patients with intermediate AMD (iAMD) or geographic atrophy (GA) secondary to nonexudative AMD in 1 eye and exudative AMD in the fellow eye., Methods: All patients were imaged using both the 3×3 mm and 6×6 mm SS OCTA fields of view (PLEX Elite 9000; Carl Zeiss Meditec, Inc, Dublin, CA). The en face slab used to detect the MNV extended from the outer retina to the choriocapillaris, and projection artifacts were removed using a proprietary algorithm., Main Outcome Measures: Prevalence of subclinical MNV and time to exudation with Kaplan-Meier cumulative estimates of exudation at 1 year., Results: From August 2014 through March 2017, 160 patients underwent SS OCTA (110 eyes with iAMD and 50 eyes with GA). Swept-source OCTA identified subclinical MNV at the time of first imaging in 23 of 160 eyes, for a prevalence of 14.4%. Six eyes demonstrated subclinical MNV during the follow-up. Of 134 eyes with follow-up visits, a total of 13 eyes demonstrated exudation, and of these 13 eyes, 10 eyes were found to have pre-existing subclinical MNV. By 12 months, the Kaplan-Meier cumulative incidence of exudation for all 134 eyes was 6.8%. For eyes with subclinical MNV at the time of first SS OCTA imaging, the incidence was 21.1%, and for eyes without subclinical MNV, the incidence was 3.6%. There was no difference in the cumulative incidence of exudation from pre-existing MNV in eyes with iAMD or GA (P = 0.847, log-rank test). After the detection of subclinical MNV, the risk of exudation was 15.2 times (95% confidence interval, 4.2-55.4) greater compared with eyes without subclinical MNV., Conclusions: By 12 months, the risk of exudation was greater for eyes with documented subclinical MNV compared with eyes without detectable MNV. For eyes with subclinical MNV, recommendations include more frequent follow-up and home monitoring. Intravitreal therapy is not recommended until prospective studies are performed., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The choriocapillaris (CC) plays an essential role in maintaining the normal functions of the human eye. There is increasing interest in the community to develop an imaging technique for visualizing the CC, yet this remains underexplored due to technical limitations. We propose an approach for the visualization of the CC in humans via a complex signal-based optical microangiography (OMAG) algorithm, based on commercially available spectral domain optical coherence tomography (SD-OCT). We show that the complex signal-based OMAG was superior to both the phase and amplitude signal-based approaches in detailing the vascular lobules previously seen with histological analysis. With this improved ability to visualize the lobular vascular networks, it is possible to identify the feeding arterioles and draining venules around the lobules, which is important in understanding the role of the CC in the pathogenesis of ocular diseases. With built-in FastTrac™ and montage scanning capabilities, we also demonstrate wide-field SD-OCT angiograms of the CC with a field of view at 9×11  mm2., ((2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).)

Purpose: We compared area measurements for the same neovascular lesions imaged using swept source optical coherence tomography angiography (SS-OCTA) and enlarging scan patterns., Methods: Patients with neovascular age-related macular degeneration were imaged using a 100-kHz SS-OCTA instrument (PLEX Elite 9000). The scanning protocols included the 3 × 3, 6 × 6, 9 × 9, and 12 × 12 mm fields of view. Two groups were studied. Group 1 included small lesions contained within the 3 \( \times \) 3 mm scan, and Group 2 included larger lesions that were fully contained within the 6 \( \times \) 6 mm scan., Results: A total of 30 eyes of 26 patients were enrolled in Group 1 and 30 eyes of 25 patients were enrolled in Group 2. In Group 1, the automated mean lesion area measurements were 1.11 (SD = 0.78), 1.14 (SD = 0.80), and 1.27 (SD = 0.82) mm2 for the 3 \( \times \) 3, 6 \( \times \) 6, and 12 \( \times \) 12 mm scans, respectively (ANOVA P < 0.001; post hoc comparisons, P = 0.184, 3 \( \times \) 3 vs. 6 \( \times \) 6 mm; P < 0.001 for the other two pairs). In Group 2, the automated mean lesion area measurements were 5.43 (SD = 2.56), 5.53 (SD = 2.48), and 5.49 (SD = 2.65) mm2 for the 6 \( \times \) 6, 9 \( \times \) 9, and 12 \( \times \) 12 mm scans, respectively (ANOVA P = 0.435; post-hoc comparisons, P = 0.062, 6 \( \times \) 6 vs. 9 \( \times \) 9 mm; P = 0.553, 6 \( \times \) 6 vs. 12 \( \times \) 12 mm; P = 0.654, 9 \( \times \) 9 vs. 12 \( \times \) 12 mm)., Conclusions: The similarity in lesion area measurements across different scan patterns suggests that SS-OCTA imaging can be used to follow quantitatively the enlargement of choroidal neovascularization as the disease progresses.

OCT has revolutionized the practice of ophthalmology over the past 10-20 years. Advances in OCT technology have allowed for the creation of novel OCT-based methods. OCT-Angiography (OCTA) is one such method that has rapidly gained clinical acceptance since it was approved by the FDA in late 2016. OCTA images are based on the variable backscattering of light from the vascular and neurosensory tissue in the retina. Since the intensity and phase of backscattered light from retinal tissue varies based on the intrinsic movement of the tissue (e.g. red blood cells are moving, but neurosensory tissue is static), OCTA images are essentially motion-contrast images. This motion-contrast imaging provides reliable, high resolution, and non-invasive images of the retinal vasculature in an efficient manner. In many cases, these images are approaching histology level resolution. This unprecedented resolution coupled with the simple, fast and non-invasive imaging platform have allowed a host of basic and clinical research applications. OCTA demonstrates many important clinical findings including areas of macular telangiectasia, impaired perfusion, microaneurysms, capillary remodeling, some types of intraretinal fluid, and neovascularization among many others. More importantly, OCTA provides depth-resolved information that has never before been available. Correspondingly, OCTA has been used to evaluate a spectrum of retinal vascular diseases including diabetic retinopathy (DR), retinal venous occlusion (RVO), uveitis, retinal arterial occlusion, and age-related macular degeneration among others. In this review, we will discuss the methods used to create OCTA images, the practical applications of OCTA in light of invasive dye-imaging studies (e.g. fluorescein angiography) and review clinical studies demonstrating the utility of OCTA for research and clinical practice., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: To image vascular features of retinitis pigmentosa (RP) using optical coherence tomography angiography (OCTA)., Methods: Patients with RP were imaged by spectral domain optical coherence tomography based angiography (OCTA). The optical microangiography (OMAG) algorithm was applied to scanned datasets to generate 3D OCTA retinal angiograms, i.e., OMAG angiograms. Motion tracking was used to minimize artifacts due to eye movement, and large field of view OMAG angiograms were achieved through a montage scanning protocol. For better visualization, depth volumes were segmented to separate the superficial retinal layers from deep outer retinal layers. The choriocapillaris and other choroidal layers were also segmented. To investigate the changes in retinal architecture, the inner segment/outer segment (IS/OS) junction to RPE layer was segmented to generate en face structural images through averaging intensity projection. Color fundus images and/or Goldmann visual fields were available for comparison of the findings to OMAG images., Results: A total of 25 eyes (13 patients, seven women and six men) diagnosed with RP at various stages were enrolled in this study from October 2014 to January 2016 and imaged by OCTA. The resulting OMAG angiograms provided detailed visualization of retinal and choroidal vascular networks presented within the retina and choroid in a large field of view (FOV) (∼6.7 mm × 6.7 mm). All patients with a severity score greater than 3 showed abnormal microvasculature in both deep retinal and choroidal layers on OMAG images. Images of patients with a score of 4 indicating only peripheral abnormalities demonstrated relatively normal vasculature networks. Microvascular changes in the retinal and choroidal vasculature correlate with structural changes in the slab from IS/OS junction to RPE layer., Conclusions: OCTA is useful in evaluating the microvascular changes in a large FOV encompassing the maculae of patients with RP. The large FOV of OMAG angiograms, enabled by the motion tracking, provides visualization of high definition and high resolution microvascular networks at varying stages of RP. Microvascular imaging may have significant utility in the diagnosis and monitoring of disease progression in RP patients.

Purpose: To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm., Methods: Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography (OMAGC) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 μm below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well., Results: Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (P = 0.61, paired t-test) and 6 × 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (P = 0.41, paired t-test) and 6 × 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (P = 0.011, paired sample t-test) and the 6 × 6-mm scans (P = 0.021, paired t-test)., Conclusions: The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.

Purpose: The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA)., Methods: Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 × 3- and 6 × 6-mm2 scans were obtained on both instruments. The 3 × 3-mm2 SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 × 6-mm2 SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 × 3-mm2 scans and twice in the 6 × 6-mm2 scans. Choroidal neovascularization was excluded if not fully contained within the 3 × 3-mm2 scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments., Results: Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 × 3-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm2, respectively (P = 0.047). For the 6 × 6-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm2 (P = 0.003)., Conclusions: The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 × 6-mm2 scans.

Purpose: Optical coherence tomography (OCT) can monitor for glaucoma by measuring dimensions of the optic nerve head (ONH) cup and disc. Multiple clinical studies have shown that different OCT devices yield different estimates of retinal dimensions. We developed phantoms mimicking ONH morphology as a new way to compare ONH measurements from different clinical OCT devices., Methods: Three phantoms were fabricated to model the ONH: One normal and two with glaucomatous anatomies. Phantoms were scanned with Stratus, RTVue, and Cirrus clinical devices, and with a laboratory OCT system as a reference. We analyzed device-reported ONH measurements of cup-to-disc ratio (CDR) and cup volume and compared them with offline measurements done manually and with a custom software algorithm, respectively., Results: The mean absolute difference between clinical devices with device-reported measurements versus offline measurements was 0.082 vs. 0.013 for CDR and 0.044 mm3 vs. 0.019 mm3 for cup volume. Statistically significant differences between devices were present for 16 of 18 comparisons of device-reported measurements from the phantoms. Offline Cirrus measurements tended to be significantly different from those from Stratus and RTVue., Conclusions: The interdevice differences in CDR and cup volume are primarily caused by the devices' proprietary ONH analysis algorithms. The three devices yield more similar ONH measurements when a consistent offline analysis technique is applied. Scan pattern on the ONH also may be a factor in the measurement differences. This phantom-based study has provided unique insights into characteristics of OCT measurements of the ONH.

Purpose: To investigate the vascular microcirculation changes in the retinal nerve fiber layer (RNFL) in normal, glaucoma suspect, and open-angle glaucoma (OAG) groups using optical coherence tomography-based microangiography (OMAG)., Methods: One eye from each subject was scanned with a Cirrus HD-OCT 5000-based OMAG prototype system montage scanning protocol centered at the optic nerve head (ONH). Blood flow signals were extracted using OMAG algorithm. Retinal nerve fiber layer vascular microcirculation was measured by calculating the blood flux index and vessel area density within a 1.2-mm width annulus centered at the ONH with exclusion of big retinal vessels. One-way ANOVA were performed to analyze the RNFL microcirculation among groups. Linear-regression models were constructed to analyze the correlation between RNFL microcirculation and clinical parameters. Discrimination capabilities of the flow metrics were assessed with the area under the receiver operating characteristic curve (AROC)., Results: Twenty normal, 26 glaucoma suspect, and 42 OAG subjects were enrolled. Eyes from OAG subjects and glaucoma suspects showed significantly lower blood flux index compared with normal eyes (P ≤ 0.0015). Retinal nerve fiber layer blood flow metrics showed significant correlations with visual field indices and structural changes in glaucomatous eyes (P ≤ 0.0123). Similar discrimination capability of blood flux index compared with RNFL thickness was found in both disease groups., Conclusions: Peripapillary RNFL vascular microcirculation measured as blood flux index by OMAG showed significant differences among OAG, glaucoma suspect, and normal controls and was significantly correlated with functional and structural defects. Retinal nerve fiber layer microcirculation measurement using OMAG may help physicians monitor glaucoma.

Optical coherence tomography angiography (OCTA) has increasingly become a clinically useful technique in ophthalmic imaging. We evaluate the repeatability and reproducibility of blood perfusion in the optic nerve head (ONH) measured using optical microangiography (OMAG)-based OCTA. Ten eyes from 10 healthy volunteers are recruited and scanned three times with a 68-kHz Cirrus HD-OCT 5000-based OMAG prototype system (Carl Zeiss Meditec Inc., Dublin, California) centered at the ONH involving two separate visits within six weeks. Vascular images are generated with OMAG processing by detecting the differences in OCT signals between consecutive B-scans acquired at the same retina location. ONH perfusion is quantified as flux, vessel area density, and normalized flux within the ONH for the prelaminar, lamina cribrosa, and the full ONH. Coefficient of variation (CV) and intraclass correlation coefficient (ICC) are used to evaluate intravisit and intervisit repeatability, and interobserver reproducibility. ONH perfusion measurements show high repeatability [CV≤3.7% (intravisit) and ≤5.2% (intervisit)] and interobserver reproducibility (ICC≤0.966) in all three layers by three metrics. OCTA provides a noninvasive method to visualize and quantify ONH perfusion in human eyes with excellent repeatability and reproducibility, which may add additional insight into ONH perfusion in clinical practice.

Optical coherence tomography angiography (OCTA) is clinically useful for the qualitative assessment of the macular microvasculature. However, there is a need for comprehensive quantitative tools to help objectively analyze the OCT angiograms. Few studies have reported the use of a single quantitative index to describe vessel density in OCT angiograms. In this study, we introduce a five-index quantitative analysis of OCT angiograms in an attempt to detect and assess vascular abnormalities from multiple perspectives. The indices include vessel area density, vessel skeleton density, vessel diameter index, vessel perimeter index, and vessel complexity index. We show the usefulness of the proposed indices with five illustrative cases. Repeatability is tested on both a healthy case and a stable diseased case, giving interclass coefficients smaller than 0.031. The results demonstrate that our proposed quantitative analysis may be useful as a complement to conventional OCTA for the diagnosis of disease and monitoring of treatment.

Purpose: To determine whether angiography with swept-source (SS) optical coherence tomography (OCT) identifies subclinical type 1 neovascularization in asymptomatic eyes with intermediate age-related macular degeneration (iAMD)., Design: Prospective, observational, consecutive case series., Participants: Patients with asymptomatic iAMD in one eye and neovascular age-related macular degeneration (AMD) in their fellow eye., Methods: The patients underwent SS OCT angiography (OCTA), fluorescein angiography (FA), and indocyanine green angiography (ICGA), and the images from these 3 angiographic techniques were compared., Main Outcome Measures: Identification of subclinical type 1 neovascularization with SS OCTA in asymptomatic eyes with iAMD., Results: Eleven consecutive patients with iAMD in one eye and neovascular AMD in their fellow eye were imaged with FA, ICGA, and SS OCTA between August 2014 and September 2015. Clinical examination of the 11 eyes revealed drusen and pigmentary abnormalities in the central macula and no evidence of macular fluid on routine OCT imaging. Ten of the 11 eyes had no evidence of leakage on FA and 1 eye had questionable fluorescein leakage. Indocyanine green angiography revealed the presence of central macular plaques in 3 of the 11 asymptomatic eyes with iAMD, and SS OCTA revealed unambiguous type 1 neovascularization corresponding to the plaques in all 3 eyes. Optical coherence tomography angiography did not identify neovascularization in the remaining 8 eyes., Conclusions: Swept-source OCTA identified type 1 neovascularization corresponding to ICGA plaques in asymptomatic eyes with iAMD. The ability of OCTA to provide noninvasive, fast, detailed, depth-resolved identification of nonexudative neovascular lesions in eyes with iAMD suggests the need for a new classification system that distinguishes between neovascular and nonneovascular iAMD., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate optic disc perfusion differences in normal, primary open-angle glaucoma (POAG), and normal tension glaucoma (NTG) eyes using optical microangiography (OMAG) based optical coherence tomography (OCT) angiography technique., Design: Cross-sectional, observational study., Subjects: Twenty-eight normal, 30 POAG, and 31 NTG subjects., Methods: One eye from each subject was scanned with a 68 kHz Cirrus HD-OCT 5,000-based OMAG prototype system centered at the optic nerve head (ONH) (Carl Zeiss Meditec Inc, Dublin, CA). Microvascular images were generated from the OMAG dataset by detecting the differences in OCT signal between consecutive B-scans. The pre-laminar layer (preLC) was isolated by a semi-automatic segmentation program., Main Outcome Measures: Optic disc perfusion, quantified as flux, vessel area density, and normalized flux (flux normalized by the vessel area) within the ONH., Results: Glaucomatous eyes had significantly lower optic disc perfusion in preLC in all three perfusion metrics (p<0.0001) compared to normal eyes. The visual field (VF) mean deviation (MD) and pattern standard deviation (PSD) were similar between the POAG and NTG groups, and no differences in optic disc perfusion were observed between POAG and NTG. Univariate analysis revealed significant correlation between optic disc perfusion and VF MD, VF PSD, and rim area in both POAG and NTG groups (p≤0.0288). However, normalized optic disc perfusion was correlated with some structural measures (retinal nerve fiber layer thickness and ONH cup/disc ratio) only in POAG eyes., Conclusions: Optic disc perfusion detected with OMAG was significantly reduced in POAG and NTG groups compared to normal controls, but no difference was seen between POAG and NTG groups with similar levels of VF damage. Disc perfusion was significantly correlated with VF MD, VF PSD, and rim area in glaucomatous eyes. Vascular changes at the optic disc as measured using OMAG may provide useful information for diagnosis and monitoring of glaucoma.

Optical coherence tomography angiography (OCTA) allows for the evaluation of functional retinal vascular networks without a need for contrast dyes. For sophisticated monitoring and diagnosis of retinal diseases, OCTA capable of providing wide-field and high definition images of retinal vasculature in a single image is desirable. We report OCTA with motion tracking through an auxiliary real-time line scan ophthalmoscope that is clinically feasible to image functional retinal vasculature in patients, with a coverage of more than 60 degrees of retina while still maintaining high definition and resolution. We demonstrate six illustrative cases with unprecedented details of vascular involvement in retinal diseases. In each case, OCTA yields images of the normal and diseased microvasculature at all levels of the retina, with higher resolution than observed with fluorescein angiography. Wide-field OCTA technology will be an important next step in augmenting the utility of OCT technology in clinical practice.

Background/purpose: To image subretinal neovascularization in proliferative macular telangiectasia Type 2 (MacTel2) using swept source optical coherence tomography based microangiography (OMAG)., Methods: Patients with macular telangiectasia Type 2 were enrolled in a prospective, observational study known as the MacTel Project and evaluated using a high-speed 1,050 nm swept-source OCT prototype system. The OMAG algorithm generated en face flow images from three retinal layers, and the region bounded by the outer retina and Bruch membrane, the choriocapillaris, and the remaining choroidal vasculature. The en face OMAG images were compared with images from fluorescein angiography and indocyanine green angiography., Results: Three eyes with neovascular macular telangiectasia Type 2 were imaged. The neovascularization was best identified from the en face OMAG images that included a layer between the outer retinal boundary and Bruch membrane. Optical coherence tomography based microangiography images identified these abnormal vessels better than fluorescein angiography and were comparable to the images obtained using indocyanine green angiography. In all 3 cases, OMAG identified choroidal vessels communicating with the neovascularization, and these choroidal vessels were evident in the 2 cases with indocyanine green angiography imaging. In 1 case, monthly injections of bevacizumab reduced the microvascular complexity of the neovascularization, and the telangiectatic changes within the retinal microvasculature. In another case, less frequent bevacizumab therapy was associated with growth of the subretinal neovascular complex., Conclusion: Optical coherence tomography based microangiography imaging provided detailed, depth-resolved information about subretinal neovascularization in macular telangiectasia Type 2 eyes demonstrating superiority to fluorescein angiography imaging, and similarities to indocyanine green angiography imaging for documenting the retinal microvascular changes, the size and extent of the neovascular complex, the communications between the neovascular complex and the choroidal circulation, and the response to monthly bevacizumab therapy.

Purpose: To evaluate longitudinal changes in circumpapillary retinal nerve fiber layer (RNFL) thickness, as measured by spectral-domain optical coherence tomography (SD OCT), in children with optic pathway gliomas., Design: Longitudinal cohort study., Methods: Global and quadrant-specific circumpapillary RNFL thickness measures were acquired using either a hand-held SD OCT during sedation or a table-top SD OCT in children old enough to cooperate. Vision loss was defined as either a 0.2 logMAR decline in visual acuity or progression of visual field. Percent change in circumpapillary RNFL thickness in eyes experiencing vision loss was compared to eyes with stable vision., Results: Fifty-five eyes completed 250 study visits. Ten eyes (18%) from 7 patients experienced a new episode of vision loss during the study and 45 eyes (82%) from 39 patients demonstrated stable vision across study visits. Percent decline of RNFL thickness between the baseline visit and first event of vision loss event was greatest in the superior (-14%) and inferior (-10%) quadrants as well as global average (-13%). Using a threshold of ≥10% decline in RNFL, the positive and negative predictive value for vision loss when 2 or more anatomic sectors were affected was 100% and 94%, respectively., Conclusions: Children experiencing vision loss from their optic pathway gliomas frequently demonstrate a ≥10% decline of RNFL thickness in 1 or more anatomic sectors. Global average and the inferior quadrant demonstrated the best positive and negative predictive values. Circumpapillary RNFL is a surrogate marker of vision and could be helpful in making treatment decisions for children with optic pathway gliomas., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: We minimized the influence of image quality variability, as measured by signal strength (SS), on optical coherence tomography (OCT) thickness measurements using the histogram matching (HM) method., Methods: We scanned 12 eyes from 12 healthy subjects with the Cirrus HD-OCT device to obtain a series of OCT images with a wide range of SS (maximal range, 1-10) at the same visit. For each eye, the histogram of an image with the highest SS (best image quality) was set as the reference. We applied HM to the images with lower SS by shaping the input histogram into the reference histogram. Retinal nerve fiber layer (RNFL) thickness was automatically measured before and after HM processing (defined as original and HM measurements), and compared to the device output (device measurements). Nonlinear mixed effects models were used to analyze the relationship between RNFL thickness and SS. In addition, the lowest tolerable SSs, which gave the RNFL thickness within the variability margin of manufacturer recommended SS range (6-10), were determined for device, original, and HM measurements., Results: The HM measurements showed less variability across a wide range of image quality than the original and device measurements (slope = 1.17 vs. 4.89 and 1.72 μm/SS, respectively). The lowest tolerable SS was successfully reduced to 4.5 after HM processing., Conclusions: The HM method successfully extended the acceptable SS range on OCT images. This would qualify more OCT images with low SS for clinical assessment, broadening the OCT application to a wider range of subjects.

Purpose: To determine the intra- and inter-visit reproducibility of ganglion cell-inner plexiform layer thickness measures using handheld optical coherence tomography (OCT) in sedated children with optic pathway gliomas and/or neurofibromatosis type 1 (NF1)., Design: Prospective longitudinal cohort study., Methods: Children with sporadic optic pathway gliomas and/or NF1 who had ≥2 volumes acquired over the macula using handheld OCT during sedation for clinically indicated magnetic resonance imaging were eligible for the intra-visit cohort. Children with repeat handheld OCT imaging within 6 months were eligible for the inter-visit cohort. Total retinal thickness and ganglion cell-inner plexiform layer thickness were measured using custom-designed automated segmentation software. Reproducibility was compared across average and anatomic quadrant by calculating the coefficient of variation (CV) and intraclass correlation coefficient (ICC)., Results: Forty-two subjects (median age 5.4 years, range 0.8-12.7 years) contributed 45 eyes to the intra-visit cohort. Thirty-one subject eyes had normal vision and 14 had abnormal vision (decreased visual acuity and/or visual field). Average and quadrant ganglion cell-inner plexiform layer measures demonstrated CVs ≤4.5% with excellent ICCs (>0.935). The superior quadrant CV differed between subjects with (4.4%) and without (2.1%) vision loss (P < .05). Twenty-five subject eyes were eligible for the inter-visit cohort, demonstrating CVs from 1.6% to 5.2%. Inter-visit ICCs were excellent (0.955-0.995)., Discussion: Handheld OCT imaging in sedated children with optic pathway gliomas produces highly reproducible measures of ganglion cell-inner plexiform layer thickness., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To determine the intra- and intervisit reproducibility of circumpapillary retinal nerve fiber layer (RNFL) measures using handheld optical coherence tomography (OCT) in sedated children., Design: Prospective cross-sectional and longitudinal study., Methods: Children undergoing sedation for a clinically indicated magnetic resonance imaging for an optic pathway glioma and/or neurofibromatosis type 1 (NF1) had multiple 6 × 6 mm volumes (isotropic 300 × 300 or nonisotropic 1000 × 100 samplings) acquired over the optic nerve. Children with 2 handheld OCT sessions within 6 months were included in the intervisit cohort. The intra- and intervisit coefficient of variation (CV) and intraclass correlation coefficient (ICC) were calculated for the average and anatomic quadrant circumpapillary RNFL thickness., Results: Fifty-nine subjects (mean age 5.1 years, range 0.8-13.0 years) comprised the intravisit cohort and 29 subjects (mean age 5.7 years, range 1.8-12.7 years) contributed to the intervisit cohort. Forty-nine subjects had an optic pathway glioma and 10 subjects had NF1 without an optic pathway glioma. The CV was comparable regardless of imaging with an isotropic and nonisotropic volume in both the intra- and intervisit cohorts. The average circumpapillary RNFL demonstrated the lowest CV and highest ICC compared to the quadrants. For the intervisit cohort, the average ICC was typically higher while the CV was typically lower, but not statistically different compared to the other quadrants., Discussion: Circumpapillary RNFL measures acquired with handheld OCT during sedation demonstrate good intra- and intervisit reproducibility. Handheld OCT has the potential to monitor progressive optic neuropathies in young children who have difficulty cooperating with traditional OCT devices., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: To test the effect of a novel signal normalization method for reducing systematic optical coherence tomography (OCT) measurement differences among multiple spectral-domain (SD) OCT devices., Methods: A total of 109 eyes from 59 subjects were scanned with two SD-OCT devices (Cirrus and RTVue) at the same visit. Optical coherence tomography image data were normalized to match their signal characteristics between the devices. To compensate signal strength differences, custom high dynamic range (HDR) processing was also applied only to images with substantially lower signal strength. Global mean peripapillary retinal nerve fiber layer (RNFL) thicknesses were then measured automatically from all images using custom segmentation software and were compared to the original device outputs. Structural equation models were used to analyze the absolute RNFL thickness difference between original device outputs and our software outputs after signal normalization., Results: The device-measured RNFL thickness showed a statistically significant difference between the two devices (mean absolute difference 10.58 μm, P < 0.05), while there was no significant difference after normalization on eyes with 62.4-μm or thicker RNFL (mean absolute difference 2.95 μm, P < 0.05)., Conclusions: The signal normalization method successfully reduces the systematic difference in RNFL thickness measurements between two SD-OCT devices. Enabling direct comparison of RNFL thickness obtained from multiple devices would broaden the use of OCT technology in both clinical and research applications.

Purpose: We developed a method to normalize optical coherence tomography (OCT) signal profiles from two spectral-domain (SD) OCT devices so that the comparability between devices increases., Methods: We scanned 21 eyes from 14 healthy and 7 glaucoma subjects with two SD-OCT devices on the same day, with equivalent cube scan patterns centered on the fovea (Cirrus HD-OCT and RTVue). Foveola positions were selected manually and used as the center for registration of the corresponding images. A-scan signals were sampled 1.8 mm from the foveola in the temporal, superior, nasal, and inferior quadrants. After oversampling and rescaling RTVue data along the Z-axis to match the corresponding Cirrus data format, speckle noise reduction and amplitude normalization were applied. For comparison between normalized A-scan profiles, mean absolute difference in amplitude in percentage was measured at each sampling point. As a reference, the mean absolute difference between two Cirrus scans on the same eye also was measured., Results: The mean residual of the A-scan profile amplitude was reduced significantly after signal normalization (12.7% vs. 6.2%, P < 0.0001, paired t-test). All four quadrants also showed statistically significant reduction (all P < 0.0001). Mean absolute difference after normalization was smaller than the one between two Cirrus scans. No performance difference was detected between health and glaucomatous eyes., Conclusions: The reported signal normalization method successfully reduced the A-scan profile differences between two SD-OCT devices. This signal normalization processing may improve the direct comparability of OCT image analysis and measurement on various devices.

Purpose: To develop and test a novel signal enhancement method for optical coherence tomography (OCT) images based on the high dynamic range (HDR) imaging concept., Methods: Three virtual channels, which represent low, medium, and high signal components, were produced for each OCT signal dataset. The dynamic range of each signal component was normalized to the full gray scale range. Finally, the three components were recombined into one image using various weights. Fourteen eyes of 14 healthy volunteers were scanned multiple times using time-domain (TD)-OCT before and while preventing blinking in order to produce a wide variety of signal strength (SS) images on the same eye scanned on the same day. For each eye, a pair of scans with the highest and lowest SS with successful retinal nerve fiber layer (RNFL) segmentation was selected to test the signal enhancement effect. In addition, spectral-domain (SD)-OCT images with poor signal qualities were also processed., Results: Mean SS of good and poor quality scans were 9.0 ± 1.1 and 4.4 ± 0.9, respectively. TD-OCT RNFL thickness showed significant differences between good and poor quality scans on the same eye (mean difference 11.9 ± 6.0 μm, P < 0.0001, paired t-test), while there was no significant difference after signal enhancement (1.7 ± 6.2 μm, P = 0.33). However, HDR had weaker RNFL compensation effect on images with SS less than or equal to 4, while it maintained good compensation effect on images with SS greater than 4. Successful signal enhancement was also confirmed subjectively on SD-OCT images., Conclusion: The HDR imaging successfully restored OCT signal and image quality and reduced RNFL thickness differences due to variable signal level to the level within the expected measurement variability. This technique can be applied to both TD- and SD-OCT images.