Muneeswar G. Nittala

Relationship between outer retinal thickness substructures and visual acuity in eyes with dry age-related macular degeneration.

PURPOSEnTo explore the correlation between outer retinal substructures and visual acuity in dry age-related macular degeneration (AMD).nnnMETHODSnAnalysis of spectral domain optical coherence tomography datasets from 100 eyes of 100 consecutive patients with dry AMD was performed. The internal limiting membrane, outer nuclear layer (ONL), external limiting membrane (ELM), inner segment-outer segment (IS-OS) junction, outer photoreceptor border, inner and outer retinal pigment epithelium (RPE) borders, and Bruchs membrane, were manually segmented by Doheny Image Reading Center (DIRC) graders. Areas, thicknesses, and volumes of RPE, IS, OS, ONL, and the total retina in the foveal central subfield were correlated with the logarithm of minimal angle of resolution (logMAR) visual acuity using univariable and multivariable regression analysis.nnnRESULTSnThe visual acuity in this group ranged from logMAR 0 to 1.3 with a mean of 0.23. Areas, thicknesses, and volumes of ONL, IS and OS, thicknesses of total retinal and RPE, and intensities of IS, OS, and RPE, showed statistically significant association (P < 0.05) with logMAR best corrected visual acuity. The highest correlations were observed for the ONL (thickness: r = -0.49, volume: -0.47, area: -0.50) and photoreceptor IS (thickness: -0.59, area: -0.63, volume: -0.53). The model with the highest correlation in this study included thicknesses of ONL, IS, OS and RPE, as well as area of ONL, IS, OS, RPE, and intensity of RPE. CONCLUSIONS. Although integrity of outer retinal substructures in the foveal central subfield correlates with visual acuity in the eyes of patients with dry AMD, the correlation is only moderate and does not fully explain the variability in acuity in these cases.

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

PURPOSEnTo 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.nnnMETHODSnFifty 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnThere 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.

Outer retinal tubulation as a predictor of the enlargement amount of geographic atrophy in age-related macular degeneration.

PURPOSEnTo determine the prognostic value of outer retinal tubulation (ORT) in the enlargement amount of geographic atrophy (GA) in eyes with age-related macular degeneration (AMD).nnnDESIGNnCohort study.nnnPARTICIPANTSnOne hundred eight fellow untreated eyes of 143 patients with GA resulting from AMD enrolled in the MAHALO study (clinicaltrials.gov identifier, NCT01229215) who completely satisfied the study term and had gradable spectral-domain optical coherence tomography (OCT) images obtained at both baseline and month 18 visits.nnnMETHODSnThe MAHALO study enrolled 143 subjects into a phase 1b/2 multicenter, randomized, single-masked, sham-injection controlled clinical trial of the safety, tolerability, and evidence of activity of lampalizumab in patients with GA associated with AMD. Spectral-domain optical coherence tomography images were obtained at multiple time points in both eyes, although only the baseline and month 18 data of the fellow (nonstudy) eyes were considered in this exploratory analysis. The Cirrus HD-OCT review software was used for automatic segmentation and measurement of GA areas, with manual correction of segmentation errors by certified OCT graders. Baseline OCT images also were assessed for the presence of ORT. The enlargement amount of GA in eyes with ORT was compared with that of eyes without ORT.nnnMAIN OUTCOME MEASURESnComparison of the enlargement amount of GA in eyes with and without ORT.nnnRESULTSnTwenty-four of these 108 eyes demonstrated evidence of ORT. The amount of enlargement of GA in eyes with ORT was significantly slower than that of eyes without ORT (1.85±0.78 vs. 2.67±1.61; Pxa0= 0.001). This difference remained significant when considering subgroups with unifocal or multifocal GA lesions, because eyes with ORT in both subgroups had a slower enlargement amount of GA than eyes without ORT (2.91±1.70 vs. 2.08±0.88 [Pxa0= 0.01], in eyes with multifocal GA lesions; and 2.24±1.40 vs. 1.63±0.57 [Pxa0= 0.02], in eyes with unifocal GA lesions).nnnCONCLUSIONSnIn eyes with ORT, GA lesions seem to enlarge at a significantly slower rate than those of eyes without ORT. The presence of ORT may need to be accounted for in longitudinal studies of GA.

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

BACKGROUND AND OBJECTIVEnTo 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.nnnPATIENTS AND METHODSnDoppler 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.nnnRESULTSnMean 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.nnnCONCLUSIONnReproducible 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.

Spectral-domain OCT and microperimeter characterization of morphological and functional changes in X-linked retinoschisis.

A case of X-linked retinoschisis with anatomic and functional issues correlated by a constellation of methods, including spectral-domain optical coherence tomography, microperimeter, electroretinography, and multifocal electroretinography, is described. This case highlights the importance of microperimetry in the presence of normal or subtle abnormalities in full-field electroretinography. The ability of spectral-domain optical coherence tomography in diagnosis and follow-up in cases with X-linked retinoschisis is demonstrated.

Correlation between retinal sensitivity and cystoid space characteristics in diabetic macular edema.

Purpose: To evaluate the correlation between retinal sensitivity and cystoid space characteristics in eyes with diabetic macular edema (DME). Materials and Methods: Prospective cross-sectional study of 22 subjects with DME (32 treatment-naïve eyes). All study subjects underwent complete ophthalmic examination, including slit-lamp biomicroscopy and dilated fundus examination. All subjects underwent spectral domain optical coherence tomography (SD-OCT) and microperimetry (MP). Intraretinal cystoid space (ICS) volume was generated after manual delineation of cystoid space boundaries using the three-dimensional-OCT software. Various SD-OCT parameters, including retinal thickness, retinal volume, cystoid space volume, cystoid space intensity, and outer retinal structure integrity, were correlated with MP parameters and best-corrected visual acuity (BCVA). Results: Subject′s mean age was 57 ± 9 years. The mean logarithm of minimum angle of resolution BCVA was 0.4 ± 0.2. The intraclass correlation coefficient for inter- and intra-grader assessment of cystoid space volume by manual delineation was 0.99 and 0.99, respectively. Mean total ICS volume was 0.4 ± 0.4 mm 3 and for the foveal center, subfield was 0.1 ± 0.1 mm 3 . Mean retinal sensitivity was 12.89 ± 10 dB; however, foveal retinal sensitivity was 12.3 ± 11.1 dB. We found no significant correlation between BCVA and total cystoid space volume (r = 0.33, P = 0.06). Correlation between total retinal sensitivity and total ICS was negative and nonsignificant (r = −0.17, P = 0.36). Correlation between foveal retinal sensitivity and foveal cystoid space intensity was moderate and marginally significant (r = −0.43, P = 0.05). Conclusion: Total cystoid space volume was not significantly correlated with BCVA or total retinal sensitivity in subjects with DME. Foveal cystoid space optical intensity was negatively correlated with foveal retinal sensitivity. These findings suggest further investigation of cystoid space characteristics in the setting of DME may be of value.