Siva Balasubramanian

Repeatability and Reproducibility of Superficial Macular Retinal Vessel Density Measurements Using Optical Coherence Tomography Angiography En Face Images

Importance The repeatability and reproducibility of quantitative metrics from optical coherence tomographic angiography (OCTA) must be assessed before these data can be confidently interpreted in clinical research and practice. Objective To evaluate the repeatability and reproducibility of OCTA-derived retinal vascular quantitative metrics. Design, Setting and Participants In this cross-sectional study, 21 healthy volunteers (42 eyes) and 22 patients with retinal disease (22 eyes), including 14 with age-related macular degeneration, 3 with epiretinal membrane, 2 with diabetic retinopathy, 2 with myopic macular degeneration, and 1 with retinal vein occlusion, were enrolled. Participants were recruited from September 1 through November 31, 2016. Each eye underwent 3 repeated scans with 3 instruments for a total of 9 acquisitions. Eyes were randomly assigned to scanning with a 3 × 3-mm or 6 × 6-mm pattern. Eyes were excluded from subsequent analysis if any acquisition had a signal strength of less than 7. Repeatability (defined as the agreement in measurements within a device) and reproducibility (defined as the agreement between devices of the same type) were assessed by intraclass correlation coefficient (ICC) and coefficient of variation. Exposures All eyes underwent scanning using 3 separate devices. Main Outcomes and Measures Vessel length density (VLD) and perfusion density (PD) of the superficial retinal vasculature. Results A total of 21 healthy volunteers (8 men and 13 women; mean [SD] age, 36 [6] years) and 22 patients with retinal disease (15 men and 7 women; mean [SD] age, 79 [9] years) underwent evaluation. Of these, 40 of 42 normal eyes and 15 of 22 eyes with retinal disease met signal strength criteria and were included in this analysis. The ICC among the 3 consecutive scans ranged from 0.82 to 0.98 for VLD and from 0.83 to 0.95 for PD. The coefficient of variation (CV) ranged from 2.2% to 5.9% for VLD and from 2.4% to 5.9% for PD. For reproducibility, the ICC ranged from 0.62 to 0.95 and the CV was less than 6% in all groups. The agreement was highest for the 3 × 3-mm pattern in the inner ring (ICC range, 0.92 [95% CI, 0.85-0.96] to 0.96 [95% CI, 0.93-0.98]) and 6 × 6-mm pattern in the outer ring (ICC range, 0.93 [95% CI, 0.86-0.97] to 0.96 [95% CI, 0.92-0.98]). Conclusions and Relevance Vessel length density and PD of the superficial retinal vasculature can be obtained from OCTA images with high levels of repeatability and reproducibility but can vary with scan pattern and location.

Choriocapillaris Imaging Using Multiple En Face Optical Coherence Tomography Angiography Image Averaging

Importance Imaging of the choriocapillaris in vivo is challenging with existing technology. Optical coherence tomography angiography (OCTA), if optimized, could make the imaging less challenging. Objective To investigate multiple en face image averaging on OCTA images of the choriocapillaris. Design, Setting, and Participants Observational, cross-sectional case series at a referral institutional practice in Los Angeles, California. From the original cohort of 21 healthy individuals, 17 normal eyes of 17 participants were included in the study. The study dates were August to September 2016. Exposures All participants underwent OCTA imaging of the macula covering a 3 × 3-mm area using OCTA software (Cirrus 5000 with AngioPlex; Carl Zeiss Meditec). One eye per participant was repeatedly imaged to obtain 9 OCTA cube scan sets. Registration was first performed using superficial capillary plexus images, and this transformation was then applied to the choriocapillaris images. The 9 registered choriocapillaris images were then averaged. Quantitative parameters were measured on binarized OCTA images and compared with the unaveraged OCTA images. Main Outcome and Measure Vessel caliber measurement. Results Seventeen eyes of 17 participants (mean [SD] age, 35.1 [6.0] years; 9 [53%] female; and 9 [53%] of white race/ethnicity) with sufficient image quality were included in this analysis. The single unaveraged images demonstrated a granular appearance, and the vascular pattern was difficult to discern. After averaging, en face choriocapillaris images showed a meshwork appearance. The mean (SD) diameter of the vessels was 22.8 (5.8) µm (range, 9.6-40.2 µm). Compared with the single unaveraged images, the averaged images showed more flow voids (1423 flow voids [95% CI, 967-1909] vs 1254 flow voids [95% CI, 825-1683], P < .001), smaller average size of the flow voids (911 [95% CI, 301-1521] µm2 vs 1364 [95% CI, 645-2083] µm2, P < .001), and greater vessel density (70.7% [95% CI, 61.9%-79.5%] vs 61.9% [95% CI, 56.0%-67.8%], P < .001). The distribution of the number vs sizes of the flow voids was skewed in both unaveraged and averaged images. A linear log-log plot of the distribution showed a more homogeneous distribution in the averaged images compared with the unaveraged images. Conclusions and Relevance Multiple en face averaging can improve visualization of the choriocapillaris on OCTA images, transforming the images from a granular appearance to a level where the intervascular spaces can be resolved in healthy volunteers.

Green emission fluorophores in eyes with atrophic age-related macular degeneration: a colour fundus autofluorescence pilot study

Background/Aims To investigate the presence of short-wave fluorophores within regions of age-related macular degeneration (AMD)-associated macular atrophy (MA) area. Methods This is a prospective, observational, cross-sectional case series. 25 eyes (18 patients) with late AMD and clinically identified MA were enrolled. Eyes were imaged using a confocal light-emitting diode blue-light fundus autofluorescence (FAF) device (EIDON, CenterVue, Padua, Italy) with 450 nm excitation wavelength and the capability for ‘colour’ FAF imaging, including both the individual red and green components of the emission spectrum. To produce images with a high contrast for isolating the green component, the red component was subtracted from the total FAF image. The main outcome measure was the presence of green emission fluorescence component (GEFC) within the MA area. Volume spectral domain optical coherence tomography (SD-OCT) scans were obtained through the macula and the OCT was correlated with the MA lesions identified on the FAF images, including regions of increased GEFC. Results Of the investigated eyes, 11 out of 25 (44.0 %) showed the absence of GEFC in the MA area, whereas 14 eyes (56.0%) were characterised by GEFC within the MA area. The presence and distribution of GEFC in the MA area correlated with the presence of hyper-reflective material over Bruch’s membrane on the corresponding SD-OCT scans. Conclusion Short-wave fluorophores, which contribute to the GEFC, are present in the MA area and appear to correspond to residual debris or drusenoid material. Short-wavelength fluorophores revealed by colour FAF imaging may warrant further study.

Variability of Retinal Thickness Measurements in Tilted or Stretched Optical Coherence Tomography Images

Purpose To investigate the level of inaccuracy of retinal thickness measurements in tilted and axially stretched optical coherence tomography (OCT) images. Methods A consecutive series of 50 eyes of 50 patients with age-related macular degeneration were included in this study, and Cirrus HD-OCT images through the foveal center were used for the analysis. The foveal thickness was measured in three ways: (1) parallel to the orientation of the A-scan (Tx), (2) perpendicular to the retinal pigment epithelium (RPE) surface in the instrument-displayed aspect ratio image (Ty), and (3) thickness measured perpendicular to the RPE surface in a native aspect ratio image (Tz). Mathematical modeling was performed to estimate the measurement error. Results The measurement error was larger in tilted images with a greater angle of tilt. In the simulation, with axial stretching by a factor of 2, Ty/Tz ratio was > 1.05 at a tilt angle between 13° to 18° and 72° to 77°, > 1.10 at a tilt angle between 19° to 31° and 59° to 71°, and > 1.20 at an angle ranging from 32° to 58°. Of note with even more axial stretching, the Ty/Tz ratio is even larger. Tx/Tz ratio was smaller than the Ty/Tz ratio at angles ranging from 0° to 54°. The actual patient data showed good agreement with the simulation. The Ty/Tz ratio was greater than 1.05 (5% error) at angles ranging from 13° to 18° and 72° to 77°, greater than 1.10 (10% error) angles ranging from 19° to 31° and 59° to 71°, and greater than 1.20 (20% error) angles ranging from 32° to 58° in the images axially stretched by a factor of 2 (b/a = 2), which is typical of most OCT instrument displays. Conclusions Retinal thickness measurements obtained perpendicular to the RPE surface were overestimated when using tilted and axially stretched OCT images. Translational Relevance If accurate measurements are to be obtained, images with a native aspect ratio similar to microscopy must be used.

Reproducibility of Macular Thickness Measurements in Eyes Affected by Dry Age-Related Macular Degeneration From Two Different SD-OCT Instruments

BACKGROUND AND OBJECTIVE To compare macular thickness measurement algorithms of two different spectral-domain optical coherence tomography (SD-OCT) devices in eyes affected by dry age-related macular degeneration (AMD). PATIENTS AND METHODS Patients with dry AMD and healthy volunteers from the retina clinic of the Doheny Eye Center - UCLA were imaged using two different SD-OCT devices: the RS-3000 Advance (Nidek, Padova, Italy) and the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). All patients had been previously diagnosed with drusen or geographic atrophy due to AMD. The commercial instrument software was used to generate the macular retinal thickness measurements, and measurements were compared between devices. RESULTS Eighty-five diseased eyes from 49 patients and 16 healthy control eyes from eight normal volunteers were included in this study. The macular thickness measurements generated by the two instruments in eyes with AMD differed significantly in mean retinal thickness in the foveal center subfield (257.34 μm ± 51.72 μm using the Nidek OCT vs. 238.20 μm ± 51.89 μm using the Cirrus OCT; P < .001). The mean difference in macular thickness between the two devices was 19.14 μm ± 5.84 μm for diseased eyes and 17.06 μm ± 5.28 μm in normal control eyes, and this was not statistically different between the two groups (P > .05). The macular thickness measurements in diseased eyes, as evaluated by the two different instruments, however, showed excellent correlation (r = 0.99; P < .001), with an intraclass correlation coefficient of 0.99 (95% confidence interval, 0.98-0.99). Post hoc evaluation of cases with larger differences also showed differences in foveal center selection and variabilities in boundary selection with specific pathology. CONCLUSION Macular thickness measurements provided by the Nidek and Cirrus OCT instruments in eyes with dry AMD are highly correlated but show a consistent difference, which may allow the use of a standard correction factor to be applied to better interrelate measurements between the devices. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:410-415.].

Interdevice comparison of retinal sensitivity assessments in a healthy population: the CenterVue MAIA and the Nidek MP-3 microperimeters

Background To compare and correlate the retinal sensitivity measurements obtained with Nidek Microperimetry-3 (MP-3) and the CenterVue Macular Integrity Assessment (MAIA) microperimeters among healthy subjects. Methods In this prospective comparative study, 31 eyes of 23 subjects underwent complete ophthalmological examination including retinal sensitivity assessments using two microperimeters, the MP-3 (Nidek Technologies) and the MAIA (CenterVue). The mean retinal sensitivity (dB) and its corresponding luminance (asb) and contrast (log units) were analysed between the two instruments. The interdevice reproducibility and level of agreement between the sensitivity values of the devices were assessed. Results The mean retinal sensitivity (dB) measured by the MP-3 (25.02±1.06 dB, range: 20.90–26.70) was significantly (p<0.0001) lower compared with the MAIA (30.68±0.74 dB, range: 28–31.84). The luminosity levels were significantly (p<0.0001) higher with the MP3 (7.75±1.31 asb, range: 6.44–9.06) compared with the MAIA (0.92±0.14 asb, range: 0.78–1.06). The contrast sensitivity was significantly higher for the MP-3 (0.94±0.33 log units, range: 0.61–1.27) compared with the MAIA (0.23±0.03 log units, range: 0.20–0.26). Despite these absolute differences, the intraclass coefficient was 0.85 (95% CI 0.70 to 0.92) between the two devices after applying a standard correction factor to each data point (MAIA sensitivity=MP-3 sensitivity+5.65) with a mean difference between MAIA and MP-3 of 0.01. Conclusion Retinal sensitivity measures higher, but luminance and contrast sensitivity measure lower for MAIA-generated values compared with the MP-3. The relationships, however, appeared fairly consistent, and application of a standard correction factor allowed the data to be inter-related, at least for normal eyes.