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To predict the development of glaucomatous visual field (VF) defects using Fourier-domain optical coherence tomography (FD OCT) measurements at baseline visit.Multicenter longitudinal observational study. Glaucoma suspects and preperimetric glaucoma participants in the Advanced Imaging for Glaucoma Study.The optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) were imaged with FD OCT. VF was assessed every 6 months. Conversion to perimetric glaucoma was defined by VF pattern standard deviation (PSD) or glaucoma hemifield test (GHT) outside normal limits on 3 consecutive tests. Hazard ratios were calculated with the Cox proportional hazard model. Predictive accuracy was measured by the area under the receiver operating characteristic curve (AUC).Of 513 eyes (309 participants), 55 eyes (46 participants) experienced VF conversion during 41 ± 23 months of follow-up. Significant (P.05, Cox regression) FD OCT risk factors included all GCC, NFL, and disc variables, except for horizontal cup-to-disc ratio. GCC focal loss volume (FLV) was the best single predictor of conversion (AUC = 0.753, P.001 for test against AUC = 0.5). Those with borderline or abnormal GCC-FLV had a 4-fold increase in conversion risk after 6 years (Kaplan-Meier). Optimal prediction of conversion was obtained using the glaucoma composite conversion index (GCCI) based on a multivariate Cox regression model that included GCC-FLV, inferior NFL quadrant thickness, age, and VF PSD. GCCI significantly improved predictive accuracy (AUC = 0.783) over any single variable (P = .04).Reductions in NFL and GCC thickness can predict the development of glaucomatous VF loss in glaucoma suspects and preperimetric glaucoma patients.

To assess the influence of varying B-scan frame-sampling densities on retinal thickness and volume measurements from spectral domain optical coherence tomography (OCT) in eyes with neovascular age-related macular degeneration (AMD). Volume OCT data (512 × 128 macular cube over 6 × 6 mm) were collected from 39 eyes with neovascular AMD. All 128 B-scans in each image set were manually segmented, allowing quantification of the neurosensory retina, subretinal fluid (SRF), subretinal hyperreflective material (SRHM), and pigment epithelium detachment (PED). Thickness maps were generated for less dense subsets of scans, ranging from every other (64 B-scans) to every 64th (2 B-scans). For each less dense subset, foveal central subfield thickness and total macular volume (TMV) were compared with values obtained using all 128 scans (considered the reference). For each parameter, the mean absolute difference compared with the reference increased with reducing B-scan density. However, these differences did not reach statistical significance until frame-sampling density was reduced to every eighth scan (ie, 16 B-scans spaced 375 μm apart) for neurosensory retina, and every fourth scan (ie, 32 B-scans spaced 188 μm apart) for SRF, SRHM, and PED. For neurosensory retina, the mean (% error) and maximum (% error) absolute differences in TMV were 0.02 mm3 (0.24%) and 0.06 mm3 (0.79%), respectively. Similarly, at a density of 32 B-scans, mean and maximum differences for SRF were 0.004 mm3 (3.47%) and 0.02 mm3 (22.22%), respectively. The mean differences for SRHM and PED were 0.01 mm3 (8.03%) and 0.01 mm3 (4.04%), respectively. A minimum of 16 equally spaced B-scans, covering a 6 × 6 mm area, appears necessary to generate retinal thickness measurements similar to those obtained using all 128 B-scans in eyes with choroidal neovascularization (CNV). When considering other CNV lesion features, a minimum of 16 B-scans for SRF and PED, and 32 B-scans for SRHM are required to generate volume maps similar to ground-truth values. These findings may have implications for the design of acquisition and grading protocols for clinical trials using OCT in neovascular AMD.

To evaluate the impact of reducing B-scan frame-sampling density on retinal thickness measurements using spectral domain optical coherence tomography (SD-OCT) in eyes with diabetic macular edema (DME).We retrospectively collected OCT data for 64 eyes of 43 patients undergoing imaging for DME using the Cirrus HD-OCT 512 × 128 macular cube protocol. For each case, raw OCT data were imported into the 3D-OCTOR software, and retinal thickness maps were generated using all 128 B-scans and for lower densities of B-scans ranging from every other scan to only four scans (every 30-s B-scan). Maps were generated before and after manual correction of retinal boundary segmentation errors. The foveal central subfield (FCS) and total macular volume (TMV) values were used to compare thickness maps of varying densities.The mean difference in FCS retinal thickness and TMV increased as the B-scan density was reduced, particularly when the density was reduced to fewer than 16 B-scans over 6 mm. At a density of 16 B-scans, the mean absolute difference in FCS thickness was 2.43 μm (0.79%), with a maximum of 10.1 μm (4.09%). At this density, the mean difference in TMV was 0.012 mm(3) (0.13%), with a maximum difference of 0.04 mm(3) (0.47%). Manual correction of OCT segmentation errors resulted in a difference in FCS thickness of ≥ 10 μm in only 12.5% of cases, with a maximum difference of 115.7 μm.A minimum of 16 equally spaced B-scans appear necessary to generate retinal thickness measurements similar to those produced using all 128 B-scans in eyes with DME. Manual correction of segmentation errors appeared to have a clinically meaningful effect in a small minority of cases. These results may have implications for the design of SD-OCT imaging and grading protocols in clinical trials of DME, particularly when using multiple SD-OCT instruments that acquire varying numbers of B-scans.

Purpose: To examine the hypotheses that in glaucomatous eyes with single-hemifield damage, retinal blood flow (RBF) is significantly reduced in the retinal hemisphere corresponding with the abnormal visual hemifield and that there are significant associations among reduced retinal sensitivity (RS) in the abnormal hemifield, RBF, and structural measurements in the corresponding hemisphere. Design: Prospective, nonrandomized, case-control study. Participants: Thirty eyes of 30 patients with glaucoma with visual field loss confined to a single hemifield and 27 eyes of 27 controls. Methods: Normal and glaucomatous eyes underwent spectral-domain optical coherence tomography (SD-OCT) and standard automated perimetry. Doppler SD-OCT with a double-circle scanning pattern was used to measure RBF. The RBF was derived from the recorded Doppler frequency shift and the measured angle between the beam and the vessel. Total and hemispheric RBF, retinal nerve fiber layer (RNFL), and ganglion cell complex (GCC) values were calculated. The RS values were converted to 1/Lambert. Analysis of variance and regression analyses were performed. Main Outcome Measures: Total and hemispheric RS, RBF, RNFL, and GCC values. Results: The total RBF (34.6� 12.2 ml/minute) and venous cross-sectional area (0.039� 0.009 mm 2 ) were reduced (P

PURPOSE To compare the measurements of drusen area from manual segmentation of color fundus photographs with those generated by an automated algorithm designed to detect elevations of the retinal pigment epithelium (RPE) on spectral domain optical coherence tomography (SD-OCT) images. METHODS Fifty eyes with drusen secondary to nonexudative age-related macular degeneration were enrolled. All eyes were imaged with a high-definition OCT instrument using a 200 × 200 A-scan raster pattern covering a 6 mm × 6 mm area centered on the fovea. Digital color fundus images were taken on the same day. Drusen were traced manually on the fundus photos by graders at the Doheny Image Reading Center, whereas quantitative OCT measurements of drusen were obtained by using a fully automated algorithm. The color fundus images were registered to the OCT data set and measurements within corresponding 3- and 5-mm circles centered at the fovea were compared. RESULTS The mean areas (± SD [range]) for the 3-mm circles were SD-OCT = 1.57 (± 1.08 [0.03-4.44]); 3-mm color fundus = 1.92 (± 1.08 [0.20-3.95]); 5-mm SD-OCT = 2.12 (± 1.55 [0.03-5.40]); and 5-mm color fundus = 3.38 (± 1.90 [0.39-7.49]). The mean differences between color images and the SD-OCT (color - SD-OCT) were 0.36 (± 0.93) (P = 0.008) for the 3-mm circle and 1.26 (± 1.38) (P < 0.001) for the 5-mm circle measurements. Intraclass correlation coefficients of agreements for 3- and 5-mm measurements were 0.599 and 0.540, respectively. CONCLUSIONS There was only fair agreement between drusen area measurements obtained from SD-OCT images and color fundus photos. Drusen area measurements on color fundus images were larger than those with SD-OCT scans. This difference can be attributed to the fact that the OCT algorithm defines drusen in terms of RPE deformations above a certain threshold, and will not include small, flat drusen and subretinal drusenoid deposits. The two approaches provide complementary information about drusen.

Noncontact retinal blood flow measurements are performed with a Fourier domain optical coherence tomography (OCT) system using a circumpapillary double circular scan (CDCS) that scans around the optic nerve head at 3.40 mm and 3.75 mm diameters. The double concentric circles are performed 6 times consecutively over 2 sec. The CDCS scan is saved with Doppler shift information from which flow can be calculated. The standard clinical protocol calls for 3 CDCS scans made with the OCT beam passing through the superonasal edge of the pupil and 3 CDCS scan through the inferonal pupil. This double-angle protocol ensures that acceptable Doppler angle is obtained on each retinal branch vessel in at least 1 scan. The CDCS scan data, a 3-dimensional volumetric OCT scan of the optic disc scan, and a color photograph of the optic disc are used together to obtain retinal blood flow measurement on an eye. We have developed a blood flow measurement software called "Doppler optical coherence tomography of retinal circulation" (DOCTORC). This semi-automated software is used to measure total retinal blood flow, vessel cross section area, and average blood velocity. The flow of each vessel is calculated from the Doppler shift in the vessel cross-sectional area and the Doppler angle between the vessel and the OCT beam. Total retinal blood flow measurement is summed from the veins around the optic disc. The results obtained at our Doppler OCT reading center showed good reproducibility between graders and methods (0.57 with visual field pattern deviation). Doppler OCT is a new method to perform rapid, noncontact, and repeatable measurement of total retinal blood flow using widely available Fourier-domain OCT instrumentation. This new technology may improve the practicality of making these measurements in clinical studies and routine clinical practice.

BACKGROUND AND OBJECTIVE: To evaluate reproducibility and intergrader agreement of total retinal blood flow (TRBF) measurements obtained by semi-automated grading of Doppler Fourier-domain optical coherence tomography (FD-OCT) scans. PATIENTS AND METHODS: Doppler FD-OCT scans were obtained from 20 eyes of 18 subjects (10 glaucomatous, 10 normal). Scans were obtained using a circumpapillary scan protocol and analyzed using the Doppler OCT of Retinal Circulation software (version 2). Two masked, independent human graders manually refined the scans, adding or deleting vessels, changing vessel boundaries, and classifying vessels as veins or arteries. TRBF was calculated automatically by software summing flow in all veins. Agreement between various vessel parameters and TRBF values generated by the graders was analyzed. RESULTS: Mean difference and mean absolute difference (± standard deviation, range) for TRBF were −0.55 (± 5.37, −8.53 to 13.6) and 3.84 (± 3.70, 0 to 13.6) μL/min, respectively, with an intraclass correlation (ICC) of 0.933 and limits of agreement (95% confidence interval [CI]) of −11.1 to +10.0. Venous area measurements showed similar levels of agreement with mean difference and mean absolute difference (± standard deviation, range) of −2.91 (± 4.29, −10.95 to 6.43) and 3.59 (± 3.70, 0 to 10.9) mm 2 with an ICC of 0.933 and limits of agreement (95% CI) were −11.3 and +05.5. The agreement for vessel identification between graders was almost perfect with a weighted kappa of 0.86. CONCLUSION: Reproducible measurements of TRBF can be obtained from Doppler OCT data using semi-automated software with manual refinement. These findings should be of value in future studies evaluating retinal blood flow in various diseases.

Methods: In the ‘‘single-angle’’ protocol, five Doppler scans were acquired at a single beam angle. In the ‘‘dual-angle’’ protocol, three scans were obtained with the OCT beam passing through the supranasal portion of the pupil and three through the infranasal portion. The data were analyzed using a custom software termed ‘‘Doppler OCT of Retinal Circulation’’ (DOCTORC) to generate TRBF measurements. In DOCTORC, the measurement of a vein was considered unreliable if the Doppler angle was less than 38 or the coefficient of variation of Doppler angle was more than 50%. If the summated area of unreliable veins was larger than 50% of total venous area, the measurement of TRBF was considered not acceptable. Results: Ten subjects were scanned with both protocols. The Doppler angle (P � 0.003, paired t-test) and Doppler shift (P� 0.035) were significantly higher in the dualangle protocol. The yield rate, percent of eyes with valid TRBF measurement, was 80% using the dual-angle protocol and 60% from single-angle protocol. An additional 42 subjects were scanned with the single-angle protocol while 84 subjects with the dualangle protocol. Unpaired tests also showed significantly better yield rate (P¼ 0.03). Conclusions: The dual-angle protocol improved Doppler shift level in OCT. This resulted in a greater percentage of cases in which TRBF could be reliably measured. Translational Relevance: The new scan protocol improved the practicality of TRBF measurement with Doppler OCT.

To determine the relationship among visual field, neural structural, and blood flow measurements in glaucoma.Case-control study. Forty-seven eyes of 42 patients with perimetric glaucoma were age-matched with 27 normal eyes of 27 patients. All patients underwent Doppler Fourier-domain optical coherence tomography to measure retinal blood flow and standard glaucoma evaluation with visual field testing and quantitative structural imaging. Linear regression analysis was performed to analyze the relationship among visual field, blood flow, and structure, after all variables were converted to logarithmic decibel scale.Retinal blood flow was reduced in glaucoma eyes compared to normal eyes (P0.001). Visual field loss was correlated with both reduced retinal blood flow and structural loss of rim area and retinal nerve fiber layer (RNFL). There was no correlation or paradoxical correlation between blood flow and structure. Multivariate regression analysis revealed that reduced blood flow and structural loss are independent predictors of visual field loss. Each dB decrease in blood flow was associated with at least 1.62 dB loss in mean deviation (P ≤ 0.001), whereas each dB decrease in rim area and RNFL was associated with 1.15 dB and 2.56 dB loss in mean deviation, respectively (P ≤ 0.03).There is a close link between reduced retinal blood flow and visual field loss in glaucoma that is largely independent of structural loss. Further studies are needed to elucidate the causes of the vascular dysfunction and potential avenues for therapeutic intervention. Blood flow measurement may be useful as an independent assessment of glaucoma severity.