What is Optic Coherence Tomography (OCT)?
OCT is a rapid, non-invasive, office-based imaging technique that provides objective quantification of retinal structures with high resolution. The OCT measurements that are clinically meaningful for MS are peri-papillary retinal nerve fiber layer (RNFL) thickness, ganglion cell layer and inner plexiform layer (GCLIPL) thickness, and macular cube volume. These measurements are calculated for each eye and for individual quadrants within each eye. Cross-sectional images are created across the optic nerve head and the macula to allow for qualitative analysis of these areas. OCT processing software compares individual measurements to age-matched controls to provide normative readouts.
What is the applicability of OCT in MS?
Most MS patients experience damage to their anterior visual system at some point in their disease course . Therefore, OCT is an effective diagnostic tool for evaluating disease activity related to MS. Damage from MS can impact the retina in multiple different ways. Optic nerve demyelination, due to clinical or subclinical optic neuropathy in MS, results in retrograde degeneration of optic nerve axons. Since these axons originate from the retinal nerve fibers, this process results in RNFL thinning which can be detected on OCT . RNFL thickness has been shown to correlate with disability, brain atrophy, and visual function in MS patients [3, 4]. Retinal nerve fiber degeneration can also lead to the death of ganglion cells and contribute to reductions in decreased GCLIPL and total macular volume as measured by OCT .
What are the limitations in using OCT for MS?
Numerous factors decrease the accuracy of OCT for MS. In certain individuals, RNFL and GCLIPL levels can vary beyond normative levels due to physiologic variation. These variations can occur between eyes in the same individual causing inter-eye asymmetry in RNFL and GCLIPL thickness. Additionally, baseline RNFL thickness levels may vary between different ethnic groups (6). There are limited OCT data for healthy pediatric controls which limits the ability to normalize OCT testing in the pediatric population (7). Retinal structures can also be impacted by other ocular pathologies including high myopia, diabetic macular edema, ischemic optic neuropathy, glaucoma, and optic disc drusen. These factors may confound the results of OCT testing and decrease the specificity for MS.
What is required to perform OCT testing?
Obtaining and interpreting OCT testing within a clinical center requires numerous specialized staff members and procedures to ensure high quality data capture, accurate interpretation of the results, and expedient reporting of emergent findings. The technical staff performing the OCT assessments must be adequately trained to use the technology. They must be able to assess the quality of a scan to determine if immediate retesting is required. Clinicians interpreting OCT tests must be trained to systematically assess the generated data. They need to be able to detect technical artifacts and incidental ophthalmological findings within the study. Numerous resources exist to aid with this assessment (8, 9). A system must be in place for the detection of non-MS related pathology. Patients with incidental findings should be referred to a retinal specialist for further evaluation.
Are there any contraindications to OCT?
There are no absolute contraindications to OCT testing. However, OCT testing requires patients to focus their gaze on a target for at least 2 seconds. In patients with impaired cognition, encephalopathy, severely decreased visual acuity, or profound nystagmus, OCT testing may not be feasible.
When should OCT be used in MS diagnosis and management?
At our center, OTC is used as an ancillary test in specific clinical situations that arise during the work up and management of MS. These clinical scenarios and the interpretation of the OCT results within each context are summarized below. In these scenarios, OCT is used as a para-clinical test to complement the neurological exam, lab studies, and MR imaging.
|Clinical scenario||Interpretation of results|
|Evaluation for possible MS||The presence of OCT alterations consistent with acute optic neuritis or chronic optic neuropathy increases our clinical suspicion for MS (see below for more information)|
|Evaluation for optic neuritis in patients with or without MS||OCT findings consistent with optic neuritis increase our clinical suspicion for optic neuritis|
|To determine the likelihood of benefit of further relapse treatment in MS patients with optic neuritis with prolonged visual symptoms||OCT testing can be repeated in patients with ongoing visual symptoms due to optic neuritis who have completed steroid treatment. If repeat OCT testing demonstrates resolution of RNFL swelling and new GCLIPL thinning, further treatment is unlikely to confer a benefit as the inflammation is likely resolved and retinal damage has already occurred. If the repeat OCT demonstrates ongoing RNFL swelling without new GCLIPL thinning, then further treatment may be beneficial|
|Screening and monitoring for MS patients on S1P receptor modulators (S1PR)||For MS patients being considered for S1PR treatment, OCT can be used to obtain a baseline measurement of macular thickness and screen for retinal pathology. OCT can be repeated if an MS patient on treatment develops visual symptoms to evaluate for macular edema|
|Patients with recurring or chronic visual symptoms with low clinical suspicion for an underlying demyelinating disorder||A normal OCT decreases the likelihood of an underlying demyelinating disorder|
|Monitoring of MS over time||Serial OCT measurements demonstrating worsening RNFL and GCLIPL thinning suggests ongoing optic nerve damage in MS|
What does OCT show in optic neuritis?
Optic neuritis demonstrates distinct changes in both the acute and chronic phases detectable on OCT (10). Acutely, optic neuritis results in increased RNFL thickness due to inflammation within the retinal nerve fibers. This swelling can persist for weeks or months. As it resolves, “pseudonormalization” occurs in which RNFL thickness decreases but stays within a normal range due to the counterbalancing effects of resolving inflammation and progressive retinal nerve fiber atrophy. After the inflammation resolves, optic nerve atrophy remains detectable as RNFL thinning. GCLIPL thinning occurs within weeks of optic neuritis and typically precedes RNFL thinning. Clinical studies have demonstrated GCLIPL thinning as early as four weeks after optic neuritis onset . Given that optic neuritis is typically unilateral, these chronic changes result in asymmetric RNFL and GCLIPL thinning in the affected eye.
How could OCT be used to support a diagnosis of MS?
OCT results consistent with acute optic neuritis or remote optic neuropathy increase the likelihood of underlying MS. Clinical optic neuritis occurs in roughly 50% of patients with MS and is found pathologically in nearly all MS patients at autopsy [12, 1]. Clinical studies have demonstrated that OCT evidence of a 5 μm intereye difference in RNFL thickness and a 4 μm intereye difference in GCIPL thickness was highly accurate for detecting prior unilateral optic neuritis .
Are there other OCT findings specific to MS?
Microcystic macular edema is an OCT finding occurring in roughly 4.7% of MS patients and 25% of NMO patients [14 ,15]. It is defined as cystic, lacunar areas of hyporeflectivity with clear boundaries seen within the retina on spectral domain OCT macular volume images, after excluding lesions due to speckling artifact . The presence of microcystic macular edema is correlated with a higher EDSS and higher MS severity scores . Emerging research indicates that thinning of the retinal inner nuclear layer (INL) and outer nuclear layer (ONL) is associated with, and occurs more rapidly in, primary and secondary progressive MS compared to relapsing remitting MS . Further clinical research is necessary to determine if INL and ONL thinning can be used as a biomarker for progressive MS.
Are there differences in OCT results in MS compared to NMO?
Compared to MS, optic neuritis related to neuromyelitis optica (NMO) results in more severe RNFL atrophy and greater inter-eye RNFL differences . Optic neuritis in NMO is more likely to be bilateral  and as mentioned above, OCT is more likely to demonstrate microcytic macular edema in NMO .
Is there variability in an OCT test depending on the machine?
There are several OCT machines available for clinical use. Studies have demonstrated significant variability between OCT machines in RNFL thickness and GCLIPL  and, therefore, we do not recommend comparing OCT results obtained on different machines. Therefore, patients should be evaluated longitudinally using the same type of OCT machine.
- Ikuta, Fusahiro, and H. M. Zimmerman. "Distribution of plaques in seventy autopsy cases of multiple sclerosis in the United States." Neurology 26.6 Part 2 (1976): 26-28.
- Naismith, R., et al., Radial diffusivity in remote optic neuritis discriminates visual outcomes. Neurology, 2010. 74(21): p. 1702-1710.
- Fisher, J.B., et al., Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis. Ophthalmology, 2006, 113(2): p. 324-332.
- Costello, F., et al., Quantifying axonal loss after optic neuritis with optical coherence tomography. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society, 2006. 59(6): p. 963-969.
- Shindler, K.S., et al., Inflammatory demyelination induces axonal injury and retinal ganglion cell apoptosis in experimental optic neuritis. Experimental eye research, 2008. 87(3): p. 208-213.
- Kelty, Patrick J., et al. "Macular thickness assessment in healthy eyes based on ethnicity using Stratus OCT optical coherence tomography." Investigative ophthalmology & visual science 49.6 (2008): 2668-2672.
- Maccora, Katia A., Shivanand Sheth, and Jonathan B. Ruddle. "Optical coherence tomography in paediatric clinical practice." Clinical and Experimental Optometry 102.3 (2019): 300-308.
- Al-Louzi, Omar, et al. "Characteristics of morphologic macular abnormalities in neuroimmunology practice." Multiple Sclerosis Journal 25.3 (2019): 361-371.
- Hardin, Joshua S., et al. "Factors affecting Cirrus-HD OCT optic disc scan quality: a review with case examples." Journal of ophthalmology 2015 (2015).
- Henderson, Andrew PD, et al. "A serial study of retinal changes following optic neuritis with sample size estimates for acute neuroprotection trials." Brain 133.9 (2010): 2592-2602.
- Cadavid, Diego, et al. "Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial." The Lancet Neurology 16.3 (2017): 189-199.
- Peng, Anjiao, et al. "Evaluation of the retinal nerve fiber layer in neuromyelitis optica spectrum disorders: a systematic review and meta-analysis." Journal of the neurological sciences 383 (2017): 108-113.
- Nolan‐Kenney, Rachel C., et al. "Optimal intereye difference thresholds by optical coherence tomography in multiple sclerosis: an international study." Annals of neurology 85.5 (2019): 618-629.
- Gelfand, Jeffrey M., et al. "Microcystic macular oedema in multiple sclerosis is associated with disease severity." Brain 135.6 (2012): 1786-1793.
- Kaufhold, Falko, et al. "Optic neuritis is associated with inner nuclear layer thickening and microcystic macular edema independently of multiple sclerosis." PloS one 8.8 (2013): e71145.
- Brar, Manpreet, et al. "Correlation between morphological features on spectral domain optical coherence tomography and angiographic leakage patterns in macular edema." Retina (Philadelphia, Pa.) 30.3 (2010): 383.
- Sotirchos, Elias S., et al. "Progressive multiple sclerosis is associated with faster and specific retinal layer atrophy." Annals of neurology 87.6 (2020): 885-896.
- Levin, Marc H., Jeffrey L. Bennett, and A. S. Verkman. "Optic neuritis in neuromyelitis optica." Progress in retinal and eye research 36 (2013): 159-171.
- Warner, C.V., et al., The impact of utilizing different optical coherence tomography devices for clinical purposes and in multiple sclerosis trials. PLoS One, 2011. 6(8): p. e22947.