Optic neuritis as an early sign of Multiple Sclerosis


The occurrence of optic neuritis (ON, visual loss) over a persons lifetime is quoted as 50%, however the occurrence of ON as the first manifestation of MS is only 20%. If you’re not careful this can lead to misdiagnosis.

Having ways of predicting those at a greater risk of going onto developing MS is therefore key. Many have looked at this in the past and this the latest iteration of it from Optic Neuritis Treatment Trial (ONTT) with 388 individuals with ON being followed up on average 16 years (range 7-17 years).

The table below demonstrates the differing risks of a certain characteristic compared to the characteristic with perceived low risk (i.e the reference characteristic). The risk that is most obvious to the eye is the presence of brain MRI lesions with >/=3 lesions having the greatest risk, followed by 1-2 lesions (see Fig 1 below).

This in isolation is not fool proof as we know a small proportion of individuals with normal brain scans can also go onto develop MS. This is seen in their modelling where having no brain lesions still has an intermediate risk of developing MS (see Fig 2b below).

So what additional factors can be used to help predict the future risk of MS? I appears that eye pain in the affected eye and previous nonspecific neurological signs can also contribute to an increased risk of developing MS in the future.

Figure: The univariable Cox proportional hazards regression model demonstrating the association of different variables with the development of clinically definite multiple sclerosis after optic neuritis.
Figure 2: Kaplan–Meier survival curves for risk groups stratified by the prognostic model. A. Overall number of cases. B. Cases without brain lesions on MRI. C. Cases with 1 or more brain lesions on MRI.

I’m still undecided whether those with 1-3 brain lesions should commence DMTs, even if it is only platform therapies (injectables, aubagio or tecfidera). I believe this is where and elevated CSF NfL test result will have the deciding vote.


J Neuroophthalmol. 2021 Oct 22. doi: 10.1097/WNO.0000000000001424. Online ahead of print.

Development of a Prognostic Model for Predicting Multiple Sclerosis After Optic Neuritis: A Secondary Analysis of Data From the Optic Neuritis Treatment Trial

Wenjing LuoXinlei DengXiaoyu XuRuitong SongMeifeng LuoHeather E MossYi Du

Background: Optic neuritis can be the initial manifestation of multiple sclerosis (MS). The purpose of this study was to develop a prognostic model for predicting the risk of MS development among patients with optic neuritis.

Methods: The data from 388 patients with optic neuritis were retrieved from the Optic Neuritis Treatment Trial (ONTT). Cox proportional hazards regression analysis was used to develop a prognostic model. The performance of the model was assessed by using Harrell’s C-index and calibration curves. The rates of MS development were estimated using the Kaplan-Meier method.

Results: Among the enrolled subjects, a total of 154 (39.7%) patients developed clinically definite MS during a median follow-up period of 15.8 years (interquartile range, 7.2-16.9 years). The factors associated with the development of MS were the presence of brain lesions as on baseline MRI, previous nonspecific neurologic symptoms, commencing low-dose corticosteroids treatment, ocular pain, and absence of optic disc/peripapillary hemorrhage. After incorporating these 5 factors into the prognostic model, a C-index of 0.72 (95% confidence interval [CI], 0.69-0.76) and good calibration curves were obtained. The C-index of the model was significantly higher than the C-indexes of any single factor (P < 0.001 in all cases). The model was able to stratify the ONTT patient cohort into 3 risk groups with significantly different intergroup rates of developing MS (rates for developing MS within a 15-year period: high-risk group, 75.7% [95% CI, 65.6%-82.9%], intermediate-risk group, 44.7% [95% CI, 31.4%-55.4%]; and low-risk group, 20.8% [95% CI, 14.2%-26.8%]; log-rank P < 0.001).

Conclusions: This prognostic model had a better prediction ability when compared with the standard practice that relies solely on using brain lesions on MRI. It can, therefore, help guide decision-making to initiate earlier disease-modifying therapy for patients with optic neuritis at risk of developing MS.

About the author

Neuro Doc Gnanapavan


  • > I’m still undecided whether those with 1-3 brain lesions should commence DMTs,

    If an MRI showed that you had 1-3 brain lesions with ON, would you want to start on a DMT right away? Would you be comfortable with taking a watch and wait approach with your own brain? This is the only question that should influence your decision.

    • There is a separate condition called relapsing optic neuritis which is not MS – you need the correct diagnosis before you proceed to treatment. Optic neuritis for this reason isn’t part of the McDonald MS criteria.

  • “The occurrence of optic neuritis (ON, visual loss) over a persons lifetime is quoted as 50%”

    Do we have any idea why the damage caused by MS can be different in different patients ie why some MSers get damage to the optic nerve and other don’t; why some MSers get more damage in the spinal cord and others get more damage in the brain; why some MSers see a rapid deterioration while others see a slower accumulation of damage? The pathologists looking at MS and the examination of CNS tissue from MSers don’t seem to have got us very far.

    • So there is a hypothesis on this and you end having to troll though the ophthalmology journals for this one. There is an interruption in axonal transport of neurofilament proteins and other synaptic proteins. This stalling likely gives worse outcome. Recently in rat EAE there was a study showing pooling of NF proteins within the retina iteslf!

  • Can you comment on how commonplace is The Pulfrich phenomenon and any possible diagnostic use? I made a google string search of 2d objects look like 3D & MS and learned about this effect. I had latency on my VEP (dismissed as noise by a pathologist dressed in neuro-ophthalmologist clothing) but I stopped explaining the 3D effect I can get to drs because I sound a bit crazy. I just close an eye if I get distracted.



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