Clinical Applications of Optical Coherence Tomography in Glaucoma

Glaucomatous optic neuropathy is characterized by specific structural and functional changes that result from the loss of retinal ganglion cells and their corresponding axons.1,2 These structural changes are evidenced clinically by thinning of the neuroretinal rim and have traditionally been evaluated by direct clinical observation of the optic disc and surrounding area, aided by stereoscopic photographs of the optic disc and photographs of the nerve fiber layer. It has been reported that structural changes precede the functional abnormalities detectable through standard automated achromatic perimetry.3,4 Studies have also shown that there is significant variability in the appearance of the optic disc among individuals5–7 and that important variability exists in its assessment among different observers.8–10

Optical coherence tomography (OCT) enhances our ability to diagnose glaucoma and its progression by generating more objective information about the ocular structures involved in the glaucomatous process. It provides imaging of the optic disc, peripapillary, and macular areas, and generates reproducible measurements of the nerve fiber layer,11,12 retinal thickness,13,14 as well as topographic measurements of the optic nerve head (ONH). Topographic measurements of the optic nerve head have been shown to be comparable to other imaging technologies.15 Studies have shown that OCT has the ability to discriminate glaucomatous from healthy eyes.16–18

The current OCT, which is characterized by increased scan rate and image resolutions up to 8 to 10 µm, offers different options for image acquisition and analysis used in glaucoma, which include retinal nerve fiber layer (RNFL), macular and ONH scans, and ONH analysis.

Retinal Nerve Fiber Layer Scans

Cross-sectional images of the peripapillary retina are obtained through a circular scan centered on the optic nerve head with a diameter of 3.4 mm using the standard and fast RNFL protocols (Fig. 18.1).

The standard RNFL scans consist of 512 A-scan measurements along the circular scan. Fast RNFL instead obtains

256 A-scan measurements along the same circular scan (Fig. 18.2). The thickness of the RNFL is calculated automatically by the software through an algorithm that determines its inner and outer limits based on the intensity of reflectivity (white lines on the OCT image).

A normative database of age-matched peripapillary retinal nerve fiber layer thickness incorporated into the software19 enhances the ability of OCT to differentiate between glaucomatous and nonglaucomatous eyes (Fig. 18.3).20 The software generates a classification using its database to indicate nerve fiber layer values that are within normal limits (within 95% confidence interval for the healthy agematched population), borderline (between 95% and 99% confidence interval) or abnormal (lower than 99% confidence interval). In addition, the data from the two eyes is superimposed in one graph to enhance our ability to detect asymmetries between them.

The average RNFL thickness is calculated for the four quadrants (temporal, superior, nasal, and inferior) and for the 12 clock hours. The average thickness, the superior maximum (Smax), and inferior maximum (Imax) values are displayed along with parameters based on their relationship.

Optic Nerve Head Scans

Optic nerve head and macular scans are composed of six linear scans in a spoke pattern separated by 30-degree intervals centered on the ONH (Fig. 18.4).

In this protocol, the disc margin is detected automatically by the software through delineating the end of the backscattering signal thought to correspond to the retinal pigment epithelium and choriocapillaris, although it can be manually altered to increase its accuracy. A parallel line 150 µm anterior to it is used to define the cup (area below) and the neuroretinal rim (area above) (Fig. 18.5).

Based on the data obtained from individual radial scans, the vertically integrated rim area reflects the total volume of rim tissue. It is calculated by multiplying the average of individual rim areas by the circumference of the disc. The horizontally integrated rim width reflects the total rim area and is

FIG. 18.1. Cross-sectional images of the peripapillary retina are obtained through a circular scan centered on the optic nerve head with a diameter of 3.4 mm. The image illustrates the location and direction of the peripapillary scan.

calculated by multiplying the average of the individual rim widths by the circumference of the disc. In addition the disc area, cup area, rim area, cup/disc area ratio, and horizontal and vertical cup/disc ratios are displayed.

Macular Thickness Scans

Macular thickness scans have a complementary role in the diagnosis and management of glaucoma. Ganglion cells are thought to constitute between 30% and 35% of the total retinal thickness at the macular area. The loss of ganglion cells in glaucoma has been demonstrated experimentally.21,22 Clinically, measuring the changes in macular thickness may prove to be of value in the assessment of glaucoma,23 and the role of OCT has been investigated.24

The macular thickness protocols, explained in detail elsewhere in this book, generate data based on six radial scans in a spoke pattern centered on the fovea, each separated by 30-degree intervals (Fig. 18.6). The data are interpolated to fill the missing areas. The retinal thickness is calculated automatically after delineating the vitreoretinal interface and the change in reflectivity that occurs above the retinal pigment epithelium corresponding to the junction of inner and outer segments of the photoreceptors.

Case 1: Normal

A healthy 69-year-old woman without contributory medical, ocular, or family history presented for routine evaluation. Her

FIG. 18.2. The image of the peripapillary retina obtained by optical coherence tomography (OCT). It is composed of a series of A-scan measurements along the circular scan.

corrected visual acuity was 20/20 in each eye, intraocular pressures were 18 mm Hg in each eye, and she had a normal ophthalmologic examination. Examination of her optic nerves (Fig. 18.7A, B) revealed sharp disc margins with healthy, pink neuroretinal rims with a cup-to-disc ratio of 0.2. Humphrey achromatic automated perimetry was reliable and full in both eyes (Fig. 18.7C, D).

Fast RNFL scan displays symmetric RNFL thickness in both eyes that is within normal limits for her age; this is indicated by the green background present on the displayed parameters (Fig. 18.8). The RNFL thickness follows the normal pattern, being thicker superotemporally and inferotemporally with minimal asymmetry between the two eyes.

Optic nerve head analysis (Fig. 18.9) shows the delineation of the disc and cup areas on the right of the display. The crosssectional scan is seen on the left of the display. A healthy and symmetric neuroretinal rim can be appreciated throughout all clock hours of her optic discs. Normal optic nerve head analysis parameters such as the vertical integrated rim area and horizontal integrated rim width are displayed as well as individual radial scan parameters. Analysis of her macular scans (Fig. 18.10) display normal retinal thickness values and patterns on both eyes. This is illustrated by the green background on the tabular output.

Case 2: Unilateral Exfoliation

A 64-year-old woman was diagnosed with unilateral exfoliative glaucoma in her right eye. She presented with intraocular pressures of 33 mm Hg in her right eye and 18 mm Hg in her left eye. Findings on slit-lamp examination were consistent with her diagnosis. Funduscopic examination revealed marked thinning of the neuroretinal rim in her right eye throughout the superior, temporal, and inferior aspects of the disc. This is in contrast to the healthy-appearing optic disc on her left eye (Fig. 18.11A, B). The Humphrey visual field of her right

eye shows classic glaucomatous abnormality with a decrease in mean deviation (MD) and an inferior arcuate scotoma (Fig. 18.11C); her left visual field was normal (Fig. 18.11D). On her RNFL thickness average analysis (Fig. 18.12), the plotted RNFL graph of the right eye shows marked statistically significant thinning at the superior and inferior poles of the disc. This finding is highlighted by the clock-hour analysis to the right of the graph. The RNFL of the left optic nerve head falls within the statistically normal values. The superimposed plots at the bottom left of the display enhances our ability to detect asymmetries between the RNFL of the optic nerves. In her case the RNFL thickness is clearly reduced when compared to the left. The absolute values of the maximum superior (Smax) and inferior (Imax) RNFL thickness as well as their average thickness (Savg and Iavg) are abnormally thin and their statistical significance is highlighted by the red background.

Case 3: Suspicious for Glaucoma

A 62-year-old woman was referred as being suspicious for glaucoma based on large cup-to-disc ratio in both eyes and a family history of glaucoma. She had normal intraocular pressures and an otherwise unremarkable ophthalmic examination. Her optic discs showed a large cup-to-disc ratio (Fig. 18.13A), although achromatic Humphrey visual fields and Humphrey frequency doubling technology perimetry (FDT) were normal (Fig. 18.13B, C).

In spite of the glaucomatous appearance of the optic nerve, analysis of the RNFL scan evidences normal thickness values throughout all clock hours (Fig. 18.14). Given the variability of normal optic nerve head sizes and shapes, OCT proves to be a valuable tool in the assessment of the peripapillary

nerve fiber layer. Optic nerve head analysis correlates well with the clinical characteristics of the optic nerve with the benefit of objectively measuring the large cup, disc size, and other parameters. In this patient, a relatively large disc area and increased cup-to-disc ratio are noted (Fig. 18.15).

The optic nerve head analysis may play a valuable role in the long-term follow-up of this patient by establishing objective baseline measurements and enhancing our ability to detect changes over time.

Case 4: Ocular Hypertension, Suspicious for Glaucoma

A patient with ocular hypertension and suspicious optic nerve heads was observed over a period of time (Fig. 18.16). Achromatic Humphrey visual fields do not show evident glaucomatous damage, and FDT results are borderline (Fig. 18.17). An OCT was performed using the RNFL scan, which showed

18. Optical Coherence Tomography in Glaucoma

borderline thickness values, alerting us with the yellow background in the display, indicating statistical significance. The thinning is more evident at the RNFL located at the superior and inferior poles of the disc (Fig. 18.18).

In this case, serial RNFL analysis proved to be very useful, indicating that the RNFL thickness remained stable over time as displayed by the superimposed plots on the graph representing the different scans (Fig. 18.19).

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Case 5: Structure Function Correlation

A 56-year-old woman with open-angle glaucoma presented with localized nerve fiber layer loss on the inferior pole of her right optic nerve head on clinical examination. Humphrey automated achromatic perimetry (Fig. 18.20) showed a dense superior glaucomatous defect that correlated well with the clinical findings.

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The RNFL scan of her right optic nerve clearly displays statistically significant thinning of the nerve fiber layer limited to the inferior pole (Fig. 18.21).

A macular scan was obtained on the same eye of the same patient, and it demonstrated thinning of the inferior macula, which correlates well with the expected loss of ganglion cells in that location, given the clinical, perimetric, and OCT RNFL findings (Fig. 18.22).

Case 6: Suspicious for Glaucoma: Detection of Early Glaucoma

A 59-year-old man was referred for a second opinion due to large suspicious optic nerves in the presence of a normal achromatic Humphrey visual field using the Swedish interactive test algorithm (SITA™). The patient denied a history of elevated intraocular pressures or family history of glaucoma. Serial diurnal intraocular pressures measured in the office were in the range of 9 to 12 mm Hg in both eyes. Examination of his anterior segment was unremarkable. Funduscopic

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exam revealed bilateral, fairly symmetric thinning of the neuroretinal rims (Fig. 18.23). This patient underwent short wavelength automated perimetry (SWAP), scanning laser polarimetry, and macular and RNFL OCT scans.

Short wavelength automated perimetry revealed a visual field defect in the form of a nasal step suggestive of glaucoma in his left eye (Fig. 18.24A, B).

An OCT was performed using first a RNFL scan (Fig. 18.25). The analysis evidenced statistically significant thinning of the RNFL in the inferior pole of both eyes, more pronounced in the left eye correlating with the observed visual field defect on SWAP.

An OCT scan of the macula also evidenced thinning of the retinal thickness inferiorly, suggesting that the extent of damage in the left eye is more advanced (Fig. 18.26). This corresponded to the location of RNFL and visual field defect observed on SWAP.

Scanning laser polarimetry was performed and confirmed the OCT findings of thinning of the RNFL in both eyes. This is in spite of a normal achromatic perimetry in the right eye (Fig. 18.27).

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Acknowledgments. The authors have no proprietary or financial interest in any products or techniques described in this chapter.

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