Ranjith Konduru

Relationship among Visual Field, Blood Flow, and Neural Structure Measurements in Glaucoma

PURPOSE To determine the relationship among visual field, neural structural, and blood flow measurements in glaucoma. METHODS 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. RESULTS Retinal blood flow was reduced in glaucoma eyes compared to normal eyes (P < 0.001). 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). CONCLUSIONS 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.

Retinal Blood Flow in Glaucomatous Eyes with Single-Hemifield Damage

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 μl/minute) and venous cross-sectional area (0.039 ± 0.009 mm(2)) were reduced (P<0.001) in those with glaucoma compared with controls (46.5 ± 10.6 μl/minute; 0.052 ± 0.012 mm(2)). Mean RBF was reduced in the abnormal hemisphere compared with the opposite hemisphere (15.3 ± 5.4 vs. 19.3 ± 8.4 μl/minute; P = 0.004). The RNFL and GCC were thinner in the corresponding abnormal hemisphere compared with the opposite hemisphere (87.0 ± 20.2 vs. 103.7 ± 20.6 μm, P = 0.002; 77.6 ± 12.1 vs. 83.6 ± 10.1 μm, P = 0.04). The RBF was correlated with RNFL (r = 0.41; P = 0.02) and GCC (r = 0.43; P = 0.02) but not the RS (r = 0.31; P = 0.09) in the abnormal hemisphere. The RBF (19.3 ± 8.4 μl/minute), RNFL (103.7 ± 20.6 μm), and GCC (83.6 ± 10.1 μm) were reduced (P<0.05) in the hemisphere with apparently normal visual field in glaucomatous eyes compared with the mean hemispheric values of the normal eyes (23.2 ± 5.3 μl/minute, 124.8 ± 9.6 μm, and 96.1 ± 5.7 μm, respectively). CONCLUSIONS In glaucomatous eyes with single-hemifield damage, the RBF is significantly reduced in the hemisphere associated with the abnormal hemifield. Reduced RBF is associated with thinner RNFL and GCC in the corresponding abnormal hemisphere. Reduced RBF and RNFL and GCC loss also are observed in the perimetrically normal hemisphere of glaucomatous eyes.

Comparison of drusen area detected by spectral domain optical coherence tomography and color fundus imaging.

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.

Reproducibility of retinal blood flow measurements derived from semi-automated Doppler OCT analysis.

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.

Predicting Development of Glaucomatous Visual Field Conversion Using Baseline Fourier-Domain Optical Coherence Tomography

PURPOSE To predict the development of glaucomatous visual field (VF) defects using Fourier-domain optical coherence tomography (FD OCT) measurements at baseline visit. DESIGN Multicenter longitudinal observational study. Glaucoma suspects and preperimetric glaucoma participants in the Advanced Imaging for Glaucoma Study. METHODS 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). RESULTS 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). CONCLUSIONS Reductions in NFL and GCC thickness can predict the development of glaucomatous VF loss in glaucoma suspects and preperimetric glaucoma patients.