Role of OCT in glaucoma

Dr samarth mishra

Various imaging techniques

• Anterior Segment:

• AS-OCT

• UBM

• Posterior Segment:

• OCT

• HRT

• GDx

• OCT is a well known and frequently used technology to image the posterior segment.

• Izatt et al. published the first report of OCT imaging of the cornea in 1994.

• In October 2005 Carl Zeiss Meditec, Inc, Dublin, CA released the Visante®, an anterior segment OCT.

• Using time domain OCT technology (TD-OCT), the Visante® creates cross-sectional images of anterior segment structures .

• It also provides measurement tools to document and follow changes in the cornea, angle, and anterior chamber.

• AS-OCT is a non-contact procedure and is more user-friendly when compared to ultrasound biomicroscopy (UBM)

• Although optic nerve damage and a progressive loss of the visual field are the final common pathways of the glaucomas, the configuration of the anterior segment is one of the most important things the clinician must assess.

• A determination of anterior segment anatomy (such as the angle grade, iris configuration, and lens position) provides essential guidance to proper clinical therapeutic decisions.

• The various ways in which physicians evaluate the anterior segment, aside from a detailed examination and gonioscopy, include technologies such as Scheimpflug photography, scanning slit-lamp systems, ultrasound biomicroscopy, and anterior segment optical coherence tomography (AS-OCT).

• Although Huang et al first described optical coherence tomography of the eye in 1991, Izatt et al described its use in the anterior segment in 1994.

• Areas in which anterior segment OCT is showing promise include :

-evaluation of the angle in glaucoma patients;

-evaluation of the cornea in refractive surgery patients—particularly LASIK patients;

-measuring the anterior chamber for certain phakic intraocular lenses; and

-as an adjunct in other operations involving the cornea, such as PTK and corneal transplants.

• Optical coherence tomography has become a powerful tool for analyzing the retina and other ocular structures.

•  Automated software segmentation algorithms are able to outline the retinal nerve fiber layer with much precision, which is relevant in glaucoma since this layer is thinned as ganglion cells are lost.

• OCT became widely popular in 2002 with the release of Stratus OCT, a time-domain technology (TD-OCT) that was well-studied and validated for use in glaucoma and retina and went on to become a standard structural imaging test.

• four years later, several companies started to release the next generation technology, spectral-domain OCT (SD-OCT), fourier-domain OCT, which improved upon TD-OCT by capturing more data in less time at a higher axial image resolution, around 5 µm.

• Ultrahigh speed swept source OCT, ultrahigh resolution OCT, polarization sensitive OCT, and adaptive optics OCT are all on the horizon.

• Currently, the most common four commercially available SD-OCT devices are: Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA, USA),

RTVue-100 (Optovue Inc., Fremont, CA, USA),

Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany), and Topcon 3D-OCT 2000 (Topcon Corporation, Tokyo, Japan).

• Each machine has different glaucoma scan patterns, proprietary software segmentation algorithms, and display outputs.

AS-OCT (For glaucoma diagnosis)

• Documents parameters such as the angle’s width, the iris’ thickness, and anterior chamber depth.

• In addition, it permits physicians to view dynamic images of the angle’s configuration under different lighting conditions.

• AS-OCT is therefore a useful adjunct in the diagnosis and treatment of glaucoma.

• Two common flaws in the performance of clinical gonioscopy include the placement of pressure on the cornea and the use of excessive amounts of light.

• Both produce the illusion of an open angle in a patient who otherwise may have narrow or even appositionally closed angles.

• AS-OCT provides little light artifact.

• It can actually dynamically show how an angle imaged in bright light may appear open but look narrow when assessed in the dark (Figure).

• The noncontact test also eliminates the problem of corneal compression.

Figure 2. AS-OCT allows the clinician to use a caliper tool to measure spaces precisely, here the angle recess.

AS-OCT of the angle in an eye with the room’s lightson (A) and then off (B). Note the appositional closure in the

dark.

• Although AS-OCT provides important information and various clues, plateau iris, or any ciliary body mediated posterior pushing of the peripheral iris (such as a cyst or tumor) cannot be diagnosed with this technology alone.

• AS-OCT is unable to image any tissues posterior to the iris due to its pigmentation.

• AS-OCT is able to show an obliterated sulcus space and angle closure in a patient with a myopic shift after routine cataract surgery and elevated IOP.

• The technology is unable to image the ciliary processes or through the pigmented iris, it can show the suprachoroidal space and effusions, another potential cause of angle closure.

AS OCT (IN GLAUCOMA SURGERY)

• AS-OCT in glaucoma surgery include the imaging of subconjunctival blebs in trabeculectomy; not only can the internal ostium be visualized but also the internal bleb structure itself.

• In tube shunt surgery, the position of the device in the anterior chamber, its proximity to the corneal endothelium, and obstructions in the lumen or irregularities in the course of the tube can be readily visualized.

• AS-OCT allows visualization of the distended Schlemm’s canal postoperatively.

• Distal intrascleral aqueous veins are sometimes visible on AS-OCT.

• AS-OCT technology can image the suprachoroidal space, thus permitting the evaluation of device success as the gold suprachoroidal microshunt . (Solx Gold Shunt; Solx, Inc., Waltham, MA).

• This device is designed to provide a conduit by which aqueous humor can exit the anterior chamber into the suprachoroidal space and thereby lower the IOP

• AS-OCT has limitations, most notably its inability to image through pigmented tissue.

• It is therefore inadequate for the assessment of the ciliary body, zonules, posterior chamber, or anterior vitreous.

Posterior segment OCT Software analyzes:

Macular Thickness Retinal Nerve Fibre Layer (RNFL) Optic Nerve Head (ONH)

Optic nerve head

Peripapillary nerve fibre layer

macular thickness

Macular Thickness Analysis• Ganglion cells- 30-35% of total retinal thickness at macula

upto 50%of ganglion cells in maculaglaucoma preferentially involves the ganglion cell complex (GCC).

Normal

Glaucoma with thinner GCC

SD-OCT Parameters

• There are three main parameters relevant to the detection of glaucomatous loss: retinal nerve fiber layer, optic nerve head, and the “ganglion cell complex.”

• The numeric values for all parameters are shaded as white, green, yellow, or red, with the yellow and red representing, < 5% and < 1%, respectively compared to the normative database.

Retinal Nerve Fiber Layer• Glaucoma is a group of many conditions sharing a final common

pathway characterized by accelerated death of retinal ganglion cells and their retinal nerve fiber layer (RNFL) axons .

• It results in characteristic visual field defects and corresponding optic nerve head anatomical changes.

• SD-OCT can directly measure and quantify RNFL thickness by calculating the area between the internal limiting membrane (ILM) and RNFL border.

• The Cirrus RNFL map represents a 6 x 6 mm cube of A-scan data centered over the optic nerve in which a 3.4 mm diameter circle of RNFL data is extracted to create what is referred to as the TSNIT map (temporal, superior, nasal, inferior, temporal). 

• It is displayed as a false color scale with the thickness values referenced to a normative database.

• The TSNIT map displays RNFL thickness values by quadrants and clock hours.

• The RNFL peaks give a sense of the anatomic distribution of nerve fiber axons represented by the superior and inferior bundles that emanate from the optic nerve. ( figure ).

• A normal RNFL curve will have the characteristic “double hump” appearance with the superior and inferior RNFL being thicker than the nasal and temporal RNFL.

• The RNFL curve is drawn as a black line on a graph featuring thickness in microns and different areas of peripapillary RNFL.

• The RNFL curve is drawn over a background of color coded areas representing RNFL thickness classification according to normative database.

RNFL analysis

Circular scanning around ONH at a radius of 1. 73mm.

Three scans are acquired and data is averaged and compared with normative data base of age matched subjects

Scan begins temporally

RNFL thickness average analysis printout -7 zones • Zone -1-Pt. I.D

• Zone -2-TSNIT with age matched normative data base

• Zone-3-TSNIT overlap of two eyes

• Zone -4-circular scan-quadrant/clockwise

• Zone-5-DATA TABLE-ratio/average

• Zone-6-RED FREE PHOTOGRAPH-position

• Zone-7-PERCENTILE COLOR CODING

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Optic Nerve Head (ONH) 

• SD-OCT also automatically outlines the optic nerve head, optic cup, and disc borders .

• Also calculates more objective measurements such as optic disc area and neuroretinal rim area in addition to the classic clinician-subjective average and vertical cup-to-disc ratios.

• Cirrus does this by defining the edge of the disc as the termination of Bruch’s membrane and then finds the shortest perpendicular distance to ILM, minimum band distance, to define the inner cup margin in each slice in a spiral around the optic disc cube data until a center is located.

• The calculated ONH parameters, except for disc area, are then compared to a normative database (figure).

• Radial line scans through optic disc provide crosssectional information on cupping and neuroretinal rim area.

Optic nerve head scans are composed of six linear scans in a spoke pattern separated by 30-degree intervals centered on the ONH

Cup/disk ratios and cup Volumes

Disc size:

by measuring the distance between the terminal ends of the choriod at the level of the pigment epithelium (green line)

Cup:

determined by drawing a line b/w both sides of the cup at a point 140um above the green line.

Area below the line is cup and above is neuroretinal rim

Ganglion Cell Analysis• The ganglion cell layer is thickest in the perimacular region and decreased total

macular thickness has been observed in glaucomatous eyes likely due to thinning of the ganglion cell layer in this region.

• Cirrus measures its Ganglion Cell Analysis (GCA) consisting of the combined ganglion cell layer (GCL) and inner plexiform layer (IPL).

• Optovue’s Ganglion Cell Complex (GCC) chose to include RNFL in their combined GCL and IPL layers.

• The Cirrus macular scan map (figure) is displayed using a similar color scale and divided into various pie sectors around the fovea.

• The calculated sectors are compared to a normative database.

• When using the average RNFL thickness at the 5% level compared to the normative database (yellow coloring on RNFL deviation map), SD-OCT has a sensitivity of 83% and a specificity of 88% compared to 80% and 94% respectively for TD-OCT.

• When using the average RNFL thickness at the 1% level (red coloring on RNFL deviation map), the specificity for both SD-OCT and TD-OCT was 100% but the sensitivity was only 65% in SD-OCT and 61% in TD-OCT.

• ONH parameters have also been found to have excellent ability to discriminate between normal eyes and eyes with even mild glaucoma.

• The parameters found to have the greatest diagnostic capability are vertical rim thickness, rim area, and vertical cup to disc ratio.

• These ONH parameters were found to be as good as RNFL thickness parameters in diagnosing glaucoma.

• Similarly, GCA parameters have been found to be comparable to ONH and RNFL parameters.

• significant structural RNFL loss occurs prior to the development of functional visual field loss.

•  In such preperimetric disease, SD-OCT RNFL is especially useful in helping to diagnose glaucoma prior to the onset of visual field loss.

• In the presence of perimetric disease, finding RNFL bundle loss on SD-OCT with a corresponding abnormality in the visual field served by those retinal ganglion cells can help confirm the diagnosis of glaucoma.

Use of SD-OCT in Detection of Glaucomatous Progression

• GPA, introduced in 2009 on the Cirrus, compares the RNFL thickness of individual clusters of A-scans, referred to as pixels, between baseline and follow up RNFL thickness maps to estimated test-retest variability. 

• Local pixels exceeding such test-retest variability are coded in yellow at the first event, and in red if the same changes are seen on three consecutive images (figure ).

• In order to generate an overall trend plot, two baseline scans with three follow up scans are necessary. 

• This linear regression line in µm/yr, representing rate of change, is drawn with an estimated confidence interval carried forward.

Progressive RNFL Thinning

• Progressive RNFL thinning measured on SD-OCT can often be used to detect progressive disease (figure).

• The top three RNFL progression patterns are:

(A) Widening of an existing RNFL defect, (B) Deepening without widening of an existing RNFL defect, or (C) Development of a new RNFL defect.

• In one study, the inferotemporal quadrant was the most frequent location for RNFL progression.

Floor Effect

• In early to moderate glaucoma, progressive thinning of RNFL thickness measured by SD-OCT is a very useful tool to judge progression of disease.

• At advanced stages however, SD-OCT is less clinically useful due to a “floor effect” of RNFL thickness.

• With advanced loss, RNFL thickness levels off, rarely falling below 50 µm and almost never below 40 µm due to the assumed presence of residual glial or nonneural tissue including blood vessels.

• At this level of disease, serial visual fields are more useful to judge progression. (figure)

Correlation of OCT with Visual Field

• Due to the variability or possible artifacts with SD-OCT measurements, all changes on OCT should be correlated with visual field changes before confirming definite progression.

• When such correspondence is not found, caution should be exercised and sources of erroneous measurements should be sought

Normative Database• As previously stated, SD-OCT measurements are compared against an age-

matched normative database.

• The normative database for the Cirrus SD-OCT consisted on 284 healthy individuals with an age range between 18 and 84 years (mean of 46.5 years).

• Ethnically, 43% were Caucasian, 24% were Asians, 18% were African American, 12% were Hispanic, 1% were Indian, and 6% were of mixed ethnicity.

• The refractive error ranged from -12.00 D to +8.00 D

• Due to this relatively small normative database and wide variation of distribution of RNFL, many results obtained by SD-OCT may be flagged as abnormal statistically in patients who are not represented in the database and thus not necessarily representing real disease.

• One should use caution to avoid overtreating “red disease” in these situations

• One common special case is the myopic patient.

• As mentioned previously, high myopes were not included in the normative database.

• Myopic eyes have thinner RNFL measurements, which can confound comparisons to the normative database.

• Additionally, myopic eyes can have unique distributions of RNFL bundles.

• With increasing myopia, the superotemporal and inferotemporal RNFL bundles tend to converge temporally.

• This may result in the temporal shift of the superior and inferior RNFL bundle peaks of normal magnitude.

• Due to this shift, although the peaks are of normal magnitude, they can be interpreted as thinned due to having a different distribution from the normative database.

• Additionally, even in normal eyes, split RNFL bundles, both superiorly and inferiorly, have been found on histologic section, thus representing a true normal variant which may appear abnormal on SD-OCT (figure).

• While the limitations of the normative database may hinder the utility of SD-OCT in diagnosing glaucoma using a single scan, serial SD-OCT scans can be very useful to judge glaucomatous progression by setting a baseline scan against which to judge progressive thinning on subsequent scans.

• Therefore, each patient can be his or her own “normative database” to diagnose glaucoma in such difficult settings as high myopia.

• Based on a longitudinal study, the age-related rate of reduction in RNFL thickness has been estimated to be -0.52 µm/year, -1.35 µm/year, and -1.25 µm/year for average, superior, and inferior RNFL respectively

Signal Quality• When assessing the adequacy of a scan, the signal strength should

always be noted.

• The signal strength, reported on a scale of 0 to 10, is defined as the averaged intensity value of the signal pixels in the OCT image.

• The best quality scans have signal strength greater than 8 (minimum acceptable scan > 6).

Blink/Saccades• An SD-OCT RNFL scan consists of multiple single A-scans side by

side to represent a B-scan cube.

• With eye movement or blinking, these scans do not align correctly which can lead to an erroneous RNFL thickness measurement, which may be misinterpreted as progressive thinning (figure).

• The new SD-OCT versions have a built-in eye tracking function which can help compensate for eye movement by relying on blood vessel registration or iris tracking.

• Using the eye tracker significantly improves the reproducibility of RNFL measurements.

Segmentation Errors• It is important to look at the segmentation lines produced by any SD-

OCT machine’s software algorithm to ensure that they are appropriately placed.

• Lines should not come together (go to zero). Occasionally, one will find that the segmentation lines are misplaced along the retina leading to errors in the calculation of RNFL thickness (figure).

• These segmentation errors are more common in the presence of poor signal strength, tilted discs, staphylomas, large peripapillary atrophy, epiretinal membranes, and posterior vitreous detachments.

• A decreased incidence of such segmentation errors in SD-OCT compared to TD-OCT.

Media Opacities

• The en face scanning laser ophthalmoscope (SLO) image should be examined to ensure the absence of a media opacity, such as a posterior vitreous detachment (PVD), within the circumpapipillary scan area.

• Areas in which data is missing due to an opacity are represented in black on the en face SLO image (figure).

• In such a case, the overlying PVD can lead to a falsely thin RNFL measurement in the underlying area.

Axial Length

• Axial length has been shown to influence SD-OCT measurements of both RNFL thickness and ONH parameters due to axial-length induced ocular magnification.

• The longer the eye, the thinner the RNFL, and the smaller the optic disc area and neuroretinal rim area.

• However, refractive error independent of axial length has not been found to affect RNFL thickness measurements as long as a well focused fundus image is obtained during scan acquisition by utilizing the Cirrus SD-OCT internal fixation focus adjustment.

• This adjustment can account for refractive errors from -20.0 D to +20.0 D

Effect of Decentration

1.

DOPPLER OCT(F-Domain)

Retinal blood flow measurement with Doppler OCT may helpus understand the role of perfusion in the causation and treatment

of glaucoma, other optic neuropathies and retinal diseases

• SD-OCT is a powerful objective structural assessment tool that can greatly assist clinicians in diagnosing and managing glaucoma (especially early disease), when used in conjunction with visual field testing and serial clinical exams.

THANK YOU