Optical Coherence Tomography in Optic Nerve Disorders

Introduction

Optical coherence tomography (OCT) is an evolving technology that provides noninvasive imaging of tissues. It uses low coherence interferometry to produce cross-sectional images based on the optical scattering of light,1 similar to ultrasound. Since its introduction into the ophthalmology clinic in the 1990s, optical coherence tomography has become a standard tool for the evaluation of ophthalmic disease. Although its main use was initially for retinal disease and glaucoma, OCT now has a niche in neuro-ophthalmic evaluation. It is mainly useful to rule in occult retinal disease when the etiology of visual loss is unclear, but it is also used to evaluate and follow up abnormalities of the retinal nerve fiber layer (RNFL), such as optic nerve edema and atrophy.2

Techniques

The Stratus OCT software (Carl Zeiss Meditec, Dublin, CA, USA) provides a variety of protocols for the evaluation of the retina. Various scanning techniques have been applied for the evaluation of optic nerve disorders.

played “unwrapped,” starting at the temporal side, followed by the superior, nasal, inferior, and finally back to the temporal side. Data are also shown in clock hours around the disc. A graph compares the measured peripapillary RNFL thickness with age-adjusted normative data3 (Figure 10.1). Measurements falling within the green area of the graph represent the 5th to 95th percentile; those falling in the yellow area of the graph represent the 1st to the 5th percentile. The red area of the graph represents RNFL below the 1st percentile. Other numerical parameters include average NFL, maximal superior nerve fiber layer thickness, maximal inferior nerve fiber layer thickness, and a ratio of the previous two parameters.3 This protocol is useful for the evaluation of optic atrophy or optic nerve edema (see Figure 10.1). The reproducibility of the Fast RNFL scan has been tested repeatedly in normal subjects and glaucoma patients with good results.4–7 It is imperative that the scanning light be centered on the optic nerve during this test. If the thickest portions of the RNFL are not in their usual superior and inferior positions along the RNFL graph (if the two “humps” appear to be shifted to the right or left), one should suspect that the circular scan has not been centered on the optic disc and the data are not accurate.

Peripapillary Retinal Nerve Fiber

Layer Scan (Fast RNFL Scan)

A 3.4-mm circular scan centered around the optic disc measures the peripapillary nerve fiber layer (NFL) thickness. The result is dis-

Papillomacular Axis Line Scan

A 10-mm linear scan from the center of the fovea through the papillomacular bundle and optic nerve provides cross-sectional visualization of

10. OCT in Optic Nerve Disorders

the full thickness of the retina and optic nerve, with a 10- m axial resolution (Figure 10.2A,B). This scan allows evaluation of the vitreo-retinal interface and individual retinal layers.3 This protocol is useful for the evaluation of the optic nerve-retinal junction where subretinal fluid may accumulate in disorders such as optic nerve pits with subretinal fluid and central serous chorioretinopathy. Although the prelaminar optic nerve is visualized, imaging is limited

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by acoustic shadowing from the dentral retinal artery and vein. Optic disc drusen also cause shadowing that may not be distinguishable from blood vessels.

Optic Disc Analysis

Serial scans in a radial orientation centered on the optic nerve are useful for evaluating the profile of the optic disc and for comparing the

FIGURE 10.2. Papillomacular line scan in patient described in Figure 10.1. The right eye (A) shows elevation of the optic nerve head when compared to

the normal left eye (B). Also note some retinal edema at the retina–optic nerve junction, seen as a triangular zone of hyporeflectivity.

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nerve fiber layer thickness in different planes. From this analysis, data of the optic nerve, disc area, cup area, and cup-to-disc ratio are calculated (Figure 10.3A,B).3 Although this protocol

J.A. Rodríguez-Padilla and T.R. Hedges III

was designed primarily for the evaluation of glaucoma,4–8 it can be useful in the evaluation of congenital optic nerve anomalies, such as pits, drusen, or papilledema.

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Macular Scans

This protocol not only provides a crosssectional image through the fovea but also gives a macular thickness analysis. The macular scan can rule out macular changes missed on the papillomacular axis line scan (see foregoing) and can define macular disease that may mimic optic neuropathy,3 including cystoid macular edema, pigment epithelial detachments, and subretinal fluid, which are visualized by this scan.

Optical Coherence Tomography

in the Analysis of Optic

Nerve Disorders

Using the peripapillary RNFL scan protocols already described, OCT can demonstrate RNFL atrophy secondary to ischemia, compression, demyelination, or increased intracranial pressure. Patterns of RNFL loss can be measured by OCT that may correlate with visual field defects. These patterns of RNFL loss may be useful in determining the location of lesions along the visual pathways. Peripapillary RNFL scans are also useful in documenting progressive changes or stability of lesions during follow-up.

Optic Disc Edema

In the evaluation of optic disc edema from various causes, including papilledema, the combination of the peripapillary nerve fiber layer scan with the papillomacular line scan (see above) is useful. In cases of optic disc swelling, the peripapillary RNFL scan will show an increase in RNFL thickness that is above the 95th percentile of the normative data that are already included in the program. RNFL thickening can be sectoral, as in some cases of anterior ischemic optic neuropathy (AION), or diffuse, as in papilledema. Resolution of disc swelling is accompanied by a return to normal of the RNFL if no permanent damage has occurred, or a decrease below the 5th percentile if RNFL loss has occurred (see Figure 10.1A,B).

J.A. Rodríguez-Padilla and T.R. Hedges III

Protocols for optic nerve analysis may also be applied in unilateral non-arteritic ischemic optic neuropathy (NAION) to evaluate the contralateral optic nerve for the “disk-at-risk” anatomy.

The line scan is useful for evaluating the presence of subretinal fluid that often accompanies optic nerve swelling in the peripapillary region and rarely in the subfoveal region, where it can cause central visual loss in some cases of papilledema from idiopathic intracranial hypertension.9 Subretinal fluid can be documented and measured by OCT in other causes of disc swelling, such as papillophlebitis and NAION (in manuscript). The papillomacular line scan can also demonstrate apparent optic disc elevation from vitreopapillary traction.10

In papilledema, OCT can be used to objectively assess peripapillary nerve fiber layer swelling and to monitor its progression to resolution or atrophy (Figure 10.4). Optical coherence tomography, using the peripapillary RNFL scan, can also help to objectively distinguish normal subjects from patients with papilledema or pseudopapilledema by showing either evolution or resolution over time in cases of papilledema, or even no changes over time with pseudopapilledema. However, it cannot distinguish mild papilledema from pseudopapilledema with a single measurement, because patients with congenitally crowded, pseudopapilledematous optic nerves have slightly thicker than normal RNFL, unless optic disc drusen develop,11 which would be associated with RNFL thinning.

Optic Atrophy

Optical coherence tomography can help rule out nerve damage, and, when normal, it allows clinicians to redirect their attention to the retina or anterior segment as the site of unexplained visual loss. In optic disc atrophy, OCT can objectively measure loss of RNFL caused by ischemic, compressive, or hereditary, nutritional, or toxic optic neuropathies. In glaucoma, loss of

RNFL, as measured by OCT, has been shown to correlate with disease progression as measured with automated perimetry.12 This finding can be extrapolated to other causes of optic

atrophy resulting from pregeniculate disease, where RNFL measurements correlate well with visual field defects, which may help localize lesions in the visual pathways, especially if the visual fields are unreliable.

In patients with compressive lesions, OCT can play a role in surgical management. It can be used to monitor progression of optic neuropathy in patients with meningiomas or to assess prognosis. For example, in cases of thyroid

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compressive optic neuropathy, normal RNFL measurements may indicate a favorable postdecompression visual prognosis. In band atrophy caused by compressive chiasmal lesions, OCT has shown a decrease in RNFL thicknesses in the nasal and temporal quadrants, as well as in the overall average RNFL thickness, that corresponds with the measured visual field loss.13,14

In acute Leber’s hereditary optic neuropathy (LHON), OCT confirms that the average RNFL is thicker than normal. OCT has also shown markedly reduced RNFL in atrophic LHON.

Among patients in whom visual recovery occurs in the atrophic stage, the average RNFL thickness has been reported to be increased compared to patients without recovery.15 Exceptions to this occurrence have been observed in our practice. Unaffected carriers of the LHON mutation have also been found to have thicker temporal RNFL than controls in one study.16 This finding also has yet to be confirmed.

In toxic optic neuropathy from ethambutol, OCT has shown a significant loss of nerve fiber layers in the temporal quadrant that is consistent with papillomacular bundle damage. The severity of RNFL loss is proportional to the visual prognosis, with more severe loss suggestive of chronic visual field loss.17

Optical coherence tomography has a possible role in the evaluation of disease progression in multiple sclerosis (MS). A recent study found decreased RNFL thickness in eyes of patients with optic neuritis secondary to MS and with MS without history of optic neuritis when compared to controls. This decrease in RNFL correlated with decrease in visual function as measured by low contrast letter acuity or contrast sensitivity.18 Based on this study, OCT may serve as a biomarker for disease activity that may assist in the evaluation of new therapies for demyelinating disease.

Optic Nerve Anomalies

In the evaluation of optic nerve anomalies,

OCT can show features that are particular to each condition. In buried optic disc drusen, OCT of the optic nerve can demonstrate shadowing.19 In eyes with optic nerve head drusen,

J.A. Rodríguez-Padilla and T.R. Hedges III

OCT can detect NFL thinning that correlates with visual field loss secondary to drusen.20

OCT may be helpful in monitoring patients who have optic disc drusen combined with increased intraocular pressure.22 In the morning glory anomaly, OCT can show a lacy pattern of cavitation in the anterior portion of the optic nerve head.19 Myelinated nerve fibers appear as thickened nerve fiber layer on OCT in affected areas of the retina.19 In superior segmental optic hypoplasia, OCT is associated with thinning of the superior peripapillary RNFL as well as the foveal RNFL. OCT can, therefore, help detect minimal degrees of hypoplasia.19,22

Optical Coherence Tomography

in the Evaluation of Occult

Retinal Disease

A discussion on the role of OCT in the diagnosis of retinal disease is extensive and beyond the scope of this chapter. However, of great interest to the neuro-ophthalmologist are retinal diseases that mimic optic nerve disease. OCT can demonstrate subtle areas of subretinal fluid, subretinal membranes, retinal thinning (holes), and preretinal membranes that might be difficult to identify or confirm by ophthalmoscopy or fluorescein angiography. To help differentiate retinopathy from optic neuropathy and identify occult retinopathy, macular scans can reveal subtle abnormalities such as macular edema, serous detachment, and pigment epithelial detachment.

A typical example of the utility of OCT in detecting retinal disease that mimics optic neuropathy is central serous retinopathy. Central serous retinopathy can usually be diagnosed by ophthalmoscopy and easily confirmed by fluorescein angiography. However, there are rare cases where OCT can show small collections of subretinal fluid that may not be seen clinically. Furthermore, OCT can be done quickly through an undilated pupil. The differentiation of central serous retinopathy from recurrent optic neuritis is important in MS patients who may experience acute visual loss while receiving corticosteroids.23

10. OCT in Optic Nerve Disorders

OCT can also be useful in the evaluation of toxic maculopathies that may be mistaken for optic neuropathies. For example, visual loss related to submacular fluid, rather than an optic neuropathy, may be distinguished by OCT in cisplatin retinopathy.19 In hydroxychloroquine retinopathy, OCT has demonstrated disruption of the photoreceptor inner/outer segment junction as well as thinning of the outer nuclear layer in severely affected patients (in manuscript). In chronic progressive eye conditions, such as retinitis pigmentosa, or after eye surgeries, such as cataract extraction, OCT can document the development of cystoid macular edema and differentiate the acute visual loss from a recent optic nerve lesion.

Conclusion

Optical coherence tomography is a new technology that allows in vivo imaging and measurement of retinal and optic nerve anatomy. For the neuro-ophthalmologist, it can provide objective measurement of the peripapillary nerve fiber layer and measure optic nerve characteristics such as the cup-to-disc ratio. It can also help prove that retinal disease is the cause of visual loss. Research prototype instruments are presently improving the resolution of optical coherence tomography.24–28 With better resolution, an even greater expansion in the application of this instrument will be seen in the future.

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