Imaging Specifications

The Cirrus 6000 is the latest OCT model from Carl Zeiss Meditec AG. Imaging specifications ⁶ include scanning speeds of 100,000 A-scans per second, an improvement over the prior model, the Cirrus 5000, which attains scanning speeds of 27–68,000 A-scans per second. For RNFL metrics, the device employs a 6.0 × 6.0 mm volume scan comprising 40,000 data points (200 horizontal B-scans each comprising 200 A-scans). The scan pattern is manually centered over the ONH. The software then derives a calculation circle with diameter estimated to be 3.46 mm and comprising 256 data points. ⁷ The calculation circle is automatically centered over the ONH by identifying the Bruch’s membrane opening (BMO) and then identifying the center of corresponding enclosed area.

Analysis

The Cirrus 6000 offers a comprehensive analysis report, the ONH and RNFL Analysis ⁶ (Fig. 7‑1c and Fig. 7‑2c). The report displays an RNFL thickness map, where cooler colors (blue and green) represent thinner RNFL and warmer colors (red and yellow) represent thicker RNFL. Thickness colors range from 0 (blue) to 350 μm (white). Adjacent to the thickness map is displayed a deviation map, which compares regions of the thickness map to an age-matched normative database. Pixels are binned into “superpixels” of 16 pixels (4 × 4 pixels) for a total of 2,500 superpixels analyzed. ⁶

The deviation map is color-coded with respect to deviation from the normative database, whereby yellow signifies an RNFL thickness seen in the bottom 1 to 5% of normals, and red signifies an RNFL thickness seen in the bottom 1% of normals. Given that 5% of normals will have yellow- or red-range RNFL thickness, out of 2,500 superpixels analyzed, approximately 125 of these can be expected to be highlighted even in normals.

In addition to the RNFL thickness and deviation maps, cpRNFL thickness measured from the calculation circle is displayed in sector grids (both four- and twelve-sector) and a thickness graph (colloquially known as a “TSNIT” graph). The thickness graph plots cpRNFL thickness as a function of the position along the optic disc circumference, with 0 degree located at the horizontal axis. The cpRNFL thickness values are compared to an age-matched normative database, with the same yellow–red percentile deviation scheme as the deviation map. For review, the calculation circle tomogram is also displayed, as is a single B-scan of the volume scan.

In the data table, the average cpRNFL thickness (around the calculation circle) and the inter-eye asymmetry are displayed. The symmetry analysis is a correlation coefficient, converted to a percentage, that compares the 256 data points of the right eye calculation circle to the corresponding points of the left eye.

Normative Database

The Cirrus RNFL and Macula Normative Database ⁶ included males or females aged 18 years or older with a normal Humphrey 24–2 SITA Standard visual field in both eyes. Ocular exclusion criteria included: best-corrected visual acuity in either eye worse than 20/40; refractive error (spherical equivalent) outside of −12.00 D to +8.00 D; presence or history of intraocular pressure ≥22 mmHg in either eye; a diagnosis of glaucoma or glaucoma suspect in either eye; an occludable angle or a history of angle-closure in either eye; presence or history of disc hemorrhage in either eye; presence of RNFL defect in either eye; presence of amblyopia in either eye; previous laser or incisional surgery; any active infection of anterior or posterior segments; or evidence of diabetic retinopathy, diabetic macular edema, or other vitreoretinal disease. Systemic exclusion criteria included: history of diabetes, leukemia, AIDS, uncontrolled systemic hypertension, dementia, or multiple sclerosis; a life-threatening or debilitating disease; current or recent (within the past 14 days) use of an agent with photosensitizing properties by any route. Images were obtained of those with a signal strength of 5 or lower, large motion artifact, >10% area of data loss, and/or a floater obstructing appropriate view.

The Cirrus RNFL and Macula Normative Database ⁶ comprises 284 subjects: 134 males and 150 females, aged 19 to 84. Only 28 subjects were aged 70 to 79, and only 3 subjects were 80 years of age or older. Thus, results in patients aged 70 or above should be interpreted with caution. The normative database also exhibits the following ethnic breakdown: 43% Caucasian, 24% Asian, 18% African-American, 12% Hispanic, 1% Indian, and 2% mixed ethnicity.

Among all variables studied, age was found to have the greatest effect on the RNFL thickness metrics. For this reason, all results are corrected for age.

Diagnostic Capability

Numerous studies have evaluated the reliability and diagnostic capabilities of cpRNFL metrics on the Cirrus, generally on prior models with similar imaging specifications and analytics, albeit with slower scanning speeds. Overall, the area under the receiver operating characteristic curve (AUC, listed parenthetically) to distinguish all-stage glaucoma from normal reaches a maximum for average (0.964, 0.950, 0.921, 0.88), superior (0.933, 0.906, 0.891, 0.88), and inferior (0.953, 0.952, 0.924, 0.87) cpRNFL thickness. ^{2 , 3 , 7 , 8} AUCs to distinguish mild glaucoma from normal were greatest for inferior (0.923, 0.895, 0.857), average (0.940, 0.893, 0.856), and superior (0.872, 0.859, 0.842) cpRNFL thickness. ^{3 , 7 , 8} Considering the specific case of preperimetric glaucoma, the parameters with the best discriminating capability were average (0.752) and inferior (0.744) cpRNFL thickness. ⁹

Additional studies have evaluated the diagnostic capability of cpRNFL thickness in myopic eyes. The parameters with the highest discriminating capabilities reside in the average (0.899) and inferior (0.906) cpRNFL thickness in highly myopic glaucomatous eyes and the average cpRNFL thickness (0.920) in nonhighly myopic eyes. ¹⁰

Standard Edition

Analysis

The principal report of the Spectralis circle scan is the RNFL Single Exam Report, ¹¹ which may be created for one eye or both eyes (Fig. 7‑3c). Similar information may also be viewed immediately during the imaging session with the Thickness Profile Tab. The RNFL Single Exam Report displays sector grids (four- and six-sector, symmetric about the vertical axis) and a thickness graph. In the sector grids, the mean RNFL thickness is indicated for each sector, as well as the global mean of all RNFL thickness values for that eye. The thickness graph plots cpRNFL thickness as a function of the position along the optic disc circumference, with 0 degree located at the intersection of the fovea-disc (FoDi) axis to the circle scan, not the horizontal axis.

Sector grids and the cpRNFL thickness graph adhere to a green–yellow–red significance scheme, whereby green color includes values present in 95% of normal subjects, yellow color indicates values present in the bottom 1 to 5% of normal subjects, and red color indicates values present in the bottom 1% of normal subjects.

An overall classification bar displays a yellow or red color if any sector in either sector grid displays a yellow or red color, respectively. In addition, a confocal scanning laser ophthalmoscopy (cSLO) image with overlaid circle scan pattern and FoDi axis, plus a circle scan tomogram, are available for review.

If a macula scan is also obtained, one may generate a combined RNFL and Asymmetry Analysis Single Exam Report, ¹¹ details of which are found in the following sections.

Glaucoma Module Premium Edition

Imaging Specifications

The Glaucoma Module Premium Edition ¹⁵ (GMPE) offers a novel “ONH-RC” scan (Fig. 7‑4e). This scan consists of three circle scans of estimated diameters 12, 14, and 16 degrees (estimated to be 3.5, 4.1, and 4.7 mm, respectively), and 24 radial scans of length 15 degrees, all automatically centered on the optic nerve using the Anatomic Positioning System (APS) (see below). ¹⁶ Each circle scan and each radial scan consist of 768 data points. The GMPE also offers the standard circle scan and volume scan available in the Standard Edition.

One unique component of the GMPE is the APS. ¹⁵ Using the APS, the ONH-RC scan itself, as opposed to the postscan analysis grid, is fixed to two structures: the foveal center and the Bruch’s membrane opening center (BMOC). All ONH-RC scans are thus automatically centered on the optic disc based on the BMOC. In addition, a line is drawn to connect these two centers to create an axis along which all scans are aligned, termed fovea-to-Bruch’s membrane opening center axis (FoBMOC). Because the ONH-RC scan consists of circle and radial scans (i.e., not a volume scan), small errors in alignment across longitudinal scans may lead to discrepancies in RNFL measurements. For this reason, proper alignment is paramount and accordingly ensured by the APS. Of importance, note that this differs from the Standard Edition circle scan, which is manually centered—thus inter-scan alignment cannot be guaranteed.

Imaging Specifications

The Avanti RTVue XR is an SD-OCT from Optovue, Inc. Specifications ¹⁹ include scanning speeds of 70,000 A-scans per second and the inclusion of two scans: a volume scan (labeled “3D Disc”) and a circle + radial scan (labeled “ONH”). The volume scan images a 6.0 × 6.0 mm area, manually centered over the ONH, and consists of 51,813 data points (101 horizontal B-scans consisting of 513 A-scans). The circle + radial scan is a manually centered scan and consists of 13 circle scans of increasing diameter and 12 radial scans. The radial scans are of length 15 degrees and each comprise 455 data points. The circle scans have diameters ranging from 1.3 to 4.9 mm (increasing by 0.3 mm increments) and comprise 425 to 965 data points, depending on the circle diameter.

Analysis

The principal RNFL thickness report is the ONH Report ¹⁹ (Fig. 7‑5c), which displays thickness values calculated along a 3.4-mm calculation circle (i.e., the cpRNFL). The report displays sector grids of various sizes (two-hemisphere, four-quadrant, and eight-sector, symmetric about the vertical and horizontal axes) with their respective cpRNFL thickness values. The eight-sector display also includes an enclosed thickness map. The average global, superior, and inferior cpRNFL thickness values, plus the difference between superior and inferior cpRNFL thickness, are displayed in a data table. In addition, a thickness graph plots cpRNFL thickness as a function of the position along the optic disc circumference, with 0 degree located along the horizontal axis.

Sector grids and the thickness graphs adhere to a green-yellow-red significance scheme, whereby green color includes values present in 95% of normal subjects, yellow color indicates values present in the bottom 1 to 5% of normal subjects, and red color indicates values present in the bottom 1% of normal subjects.

A cSLO image with overlaid thickness map and circle scan (corresponding to the diameter used for cpRNFL thickness measurements), plus a representative tomogram of the aforementioned circle scan, are available for review. If circle + radial scans are obtained for both eyes, an OU Report may be generated, which additionally displays inter-eye differences of various metrics.

Normative Database

The RTVue Normative Database ¹⁹ for the circle + radial (“ONH”) scan of the Avanti RTVue XR consists of 649 eyes from 366 subjects, with a mean age of 49.9 and an age range of 19 to 84 years. Ethnicity percentages included Caucasian (34%), Asian (22%), Hispanic (12%), African Descendant (19%), Indian/Middle Easterner (12%), Pacific Islander (0%), and other (1%). Mean sphere was −0.46 ± 1.9 D (range −7.75 D to +5.50 D).

Inclusion criteria included: age ≥18, refractive error of +8.00 D to −8.00 sphere and +2.00 to −2.00 D cylinder, and best-corrected visual acuity of 20/30 or better in each eye. Exclusion criteria included: a history of leukemia, AIDS, dementia, or multiple sclerosis; concomitant use of hydroxychloroquine or chloroquine; a family history of glaucoma among first-degree relatives; intraocular pressure of ≥22 mmHg or greater in either eye; a visual field demonstrating positive results (>30% false-negative responses, >30% false-positive responses, or >30% fixation losses, pattern standard deviation of p < 5% or worse, and/or a glaucoma hemifield test outside normal limits); active ocular disease including degenerative myopia; previous diagnosis of glaucoma or glaucoma suspect; congenital intraocular surgery or laser treatment (other than refractive surgery or uncomplicated cataract surgery greater than 6 months prior); and/or an anatomically narrow angle.

Correlational analyses revealed that decreased RNFL thickness was associated with increasing age and decreasing optic disc size. For this reason, all clinical data comparisons to the normative database are adjusted for age and optic disc size.

Diagnostic Capability

As measured by the area under the receiver operating characteristic curve (AUC, listed parenthetically in the following section), the capabilities of the Avanti SD-OCT to distinguish all-stage glaucoma from normal reach a maximum for average (0.968, 0.919, 0.87, 0.879) and inferior (0.947, 0.884, 0.86) cpRNFL thickness. ^{2 , 3 , 20 , 21} The capability to distinguish mild or preperimetric glaucoma from normal remains excellent though slightly decreased compared to that for all-stage glaucoma. ^{3 , 22} Of note, in highly myopic eyes, the diagnostic capability of cpRNFL has been shown to decline compared to emmetropic eyes. ⁴

Imaging Specifications

The 3D OCT series from Topcon Corporation includes the 3D OCT-2000 and the 3D OCT-1 Maestro2, the latter being the latest model in this series. The OCT-2000 ²³ attains scanning speeds of 50,000 A-scans per second. The OCT-2000 offers two scans: a volume scan, labeled “3D 6.0×6.0,” and a circle scan, labeled “Circle 3.40.” The volume scan consists of a manually centered 6.0 × 6.0 mm scan consisting of 65,536 data points (128 horizontal B-scans, each consisting of 512 A-scans). The volume scan derives a peripapillary calculation circle of 3.4 mm diameter. The standalone circle scan consists of a 3.4-mm-diameter circle with 1,024 data points and is automatically centered using the optic disc auto-search function, which identifies the optic disc center through registration to both infrared and color fundus photographs.

The 3D OCT-1 Maestro2 ²⁴ is the latest SD-OCT model from Topcon Corporation. The device attains scanning speeds of 50,000 A-scans per second. The OCT-1 Maestro2 offers a single scan: a manually centered 6.0 × 6.0 mm volume scan consisting of 65,536 data points (128 horizontal B-scans, each consisting of 512 A-scans). The software derives a peripapillary circle of 3.4 mm diameter composed of 1,024 data points and automatically centered on the optic disc using the retinal pigment epithelium (RPE) edge as the optic disc margin.