The Role of Optical Coherence Tomography in Neuro-Ophthalmology

Optical coherence tomography (OCT) is part of the recent wave of advances in ocular imaging that has introduced new opportunities to visualize ocular anatomy and quantify the effects of retinal nerve fiber layer (RNFL) damage. The RNFL represents the most proximal region of the afferent visual pathway, and retrobulbar damage to the optic nerve causes retrograde axonal degeneration, which manifests as visible RNFL defects and optic disc pallor. OCT employs low-coherence interferometry to generate non-invasive, in vivo, high resolution (<10µm), cross sectional images of the RNFL by measuring backscatter of infrared light. The technique is analogous to ultrasound, except that the time of flight delay is measured for light instead of sound.^1-3 OCT can reliably quantify RNFL thinning correlating to axon loss in glaucoma and other optic neuropathies, and OCT-measured RNFL values correlate well with tests of visual function.^3-9 It has been postulated that OCT may help define the structural effects of central nervous system disorders on the afferent visual pathway.

Weighing the Evidence

In an effort to quantify the structural effects of optic nerve damage, interest has focused upon the RNFL, which contains retinal ganglion cells and non-myelinated axons that comprise the optic nerve. Visible detection of RNFL atrophy requires loss of 50% of neural tissue in an affected retinal area (Arch Ophthalmol. 1982;100:807-814). Therefore, the ability of even experienced observers to quantify optic nerve damage in the clinical setting is sub-optimal, and prior attempts to study RNFL defects with ophthalmoscopy, fundus photography, and pathological techniques have been limited by the qualitative nature of the evaluation.

While the clinical impact of OCT has been fairly robust in the evaluation of glaucomatous optic neuropathies, the technology has exerted more modest,yet palpable reverberations in neuro-ophthalmic practice to date. Recent publications have highlighted the potential role for OCT as a candidate structural biomarker for axon loss in the study of optic neuritis (ON) and multiple sclerosis (MS).^4-8 In a pilot study Parisi and colleagues used OCT to compare RNFL values between 14 MS patients and normal control subjects. They reported a significant reduction in RNFL measures among MS patients and a predilection for RNFL thinning in the maculopapillary nerve fiber bundle (Invest Ophthalmol Vis Sci. 1999;40:2520-2527). A second study compared RNFL measures to tests of visual function among 25 patients with incomplete recovery after ON and reported reduced RNFL values, which correlated with diminished visual acuity, color vision, and visual field function among patients (Ann Neurol. 2005;58:383-391). A follow up study on this cohort demonstrated a correlation between reduced RNFL values (mean decrease 33% versus controls), visual function scores, and magnetic resonance imaging (MRI) measures of optic atrophy (mean decrease 30% versus controls). From their findings, Trip and associates inferred that axonal loss due to post-inflammatory brain lesions may contribute to global MRI measures of brain atrophy in MS (Neuroimage. 2006; 31:286-293). Fisher reported the results of OCT testing in a heterogenous MS cohort, which included 90 MS patients (with and without a history of ON) and 36 disease free controls. The average RNFL thickness was significantly reduced in all MS eyes as compared to normal subjects, with the lowest RNFL values noted in MS patients with a prior clinical history of ON. Lower visual function scores were also associated with reduced mean RNFL thickness in MS eyes such that for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 microns (mm) (Ophthalmology. 2006;113:324-332). Finally, in a prospective study of 54 patients with ON, significant RNFL thinning occurred in the majority (74%) of clinically affected eyes, often within 3 to 6 months of the acute event. Patients with incomplete recovery of visual field function demonstrated greater RNFL loss after ON as compared to patients with better visual outcomes, and regression analyses demonstrated a potential threshold of RNFL thickness (75 mm), below which RNFL measurements predicted persistent visual field dysfunction (Ann Neurol. 2006;59:963-969).

Additional Uses for OCT

The potential role for OCT in the investigation of compressive optic neuropathies has also been evaluated.^9,11,12 A cross sectional, retrospective study evaluated RNFL values in 34 eyes with bitemporal hemianopia caused by optic chiasm compression. The RNFL thickness in eyes with band atrophy was decreased in all OCT parameters, and the degree of RNFL thickness reduction correlated with visual field dysfunction (Ophthalmology. 2004;111:2278-2283). OCT testing also detected a pattern of RNFL loss, which correlated with band atrophy in 2 patients with longstanding bitemporal visual field defects secondary to pituitary lesions (Arq Bras Oftalmol. 2006;69:251-254). Monteiro and colleagues used OCT to study 16 patients with optic chiasm compression and reported lower overall and quadrant RNFL measures in the patients with band atrophy as compared to control patients (Ophthalmol. 2004;88:896-899). Recent reports have also documented OCT measured RNFL changes among patients with optic disc drusen (Curr Eye Res. 2003;26:277-280 & Am J Ophthalmol. 2006;141:248-253), ethambutol-induced optic neuropathy (Graefes Arch Clin Exp Ophthalmol. 2005;243:410-416), Leber’s hereditary optic neuropathy (Ophthalmology. 2005;112:120-126), and segmental optic disc hypoplasia (Br J Ophthalmol. 2002;86:910-914).

Karam and Hedges compared RNFL measures between 13 patients with mild papilledema, 11 patients with congenitally crowed optic nerves, and 17 normal subjects. They concluded that OCT showed measurable increases in RNFL thickness between normal subjects and patients with either papilledema or pseudopapilledema but failed to differentiate congenitally crowded optic nerves from those with mild papilloedema (Br J Ophthalmol. 2005;89:294-298). Lastly, in a case report progressive RNFL thinning was measured up to 70 days after an acute traumatic optic nerve injury, which showed that OCT could be used to monitor longitudinal effects of axonal degeneration in optic neuropathies (Am J Ophthalmol. 2003;135:406-408).

Future Directions

Neuro-ophthalmology is a discipline, which explores the relationship between vision and the central nervous system, and encompasses the pathological processes of the optic nerve. The clinical hallmarks of optic nerve injury include loss of visual acuity, color vision deficits, a relative afferent pupil defect, and a pattern of visual field disturbance, which corresponds to the topographical distribution of axons within the RNFL (Lancet. 2002;360:1953-1962). Acute retrobulbar optic nerve injuries often present with a normal fundus examination or mild optic disc swelling. Optic disc pallor may eventually evolve as a “footprint” of the original insult, but this ubiquitous clinical finding is not diagnostic with respect to cause, nor does it predict to what extent visual recovery will ensue after an optic nerve injury.

There is emerging evidence to suggest that OCT may be used to monitor optic nerve axonal integrity in a variety of pathological processes. Ideally, OCT measured RNFL values could help monitor the effects of regenerative strategies in inflammatory optic neuropathies and even predict the potential visual recovery or lack thereof in the preoperative evaluation of compressive optic nerve lesions. Yet, there is much to be ascertained about the sensitivity of OCT to detect relevant, subclinical optic nerve damage across a spectrum of optic neuropathies. If OCT is to be embraced as a useful technology by neuro-opthalmologists, it should improve upon current methods of assessing optic neuropathies. Otherwise, pundits may argue that technological advancements of this nature provide an expensive means to magnify uncertainty with little practical yield in the clinical setting. Efforts are ongoing to more clearly determine whether RNFL values correlate with other candidate biomarkers in advancing ocular imaging, non-conventional MRI, and visual evoked potential technology. As the role of OCT in neuro-ophthalmology continues to evolve, the ophthalmic community will await the results of future studies with a sense of cautious optimism and anticipation.

References

Author Disclosure

The author states that she has no financial relationship with the manufacturer or provider of any product or service discussed in this article or with the manufacturer or provider of any competing product or service.