OCT and evoked potentials

Why the eye

The retina is part of the brain. Its ganglion cells send their axons across the inner surface of the retina, in the retinal nerve fibre layer, to the optic disc, where they leave the eye as the optic nerve. Inside the eye these axons have no myelin. Behind the eye, in the optic nerve, they gain myelin and become a frequent target of MS, and optic neuritis is often the first symptom. Thinning of the nerve fibre layer therefore shows loss of axons, without the confusion of myelin changes, in a place that can be scanned in minutes.

Optical coherence tomography

OCT works like ultrasound but with near-infrared light. It takes a few minutes, does not touch the eye and needs no injection. It measures the thickness of the retina's layers in micrometres. Two measures matter most in MS: the peripapillary retinal nerve fibre layer (pRNFL), a ring of axons around the optic disc, and the ganglion cell and inner plexiform layer (GCIPL) at the macula, which contains the nerve cells those axons come from.

After optic neuritis, the nerve fibre layer thins over the following months. A meta-analysis of 40 studies with 5,776 eyes of people with MS found the pRNFL thinner by about 20 micrometres in eyes that had optic neuritis and by about 7 micrometres in eyes that had not, compared with healthy eyes. The GCIPL was thinner by about 16 and 6 micrometres. The authors recommended both measures for diagnosis, monitoring and research.[1] Thinning in eyes that never had optic neuritis shows that OCT captures silent damage along the visual pathway and, to some extent, throughout the brain.

The thickness of the nerve fibre layer also predicts the future. In 879 people with MS followed for a median of two years, those with a pRNFL of 87 or 88 micrometres or less, depending on the device, had twice the risk of disability worsening in the first three years, and almost four times the risk in years three to five.[2] In the 2024 McDonald criteria the optic nerve became a fifth site for showing damage in space.[3]

Evoked potentials

Evoked potentials time how long a signal takes to travel along a pathway. For visual evoked potentials, the person looks at a black and white checkerboard whose squares swap colour about twice a second, while electrodes on the back of the head record the brain's response. The main peak arrives at about 100 milliseconds and is called the P100.

In 1972, Halliday and colleagues in London showed that after optic neuritis this response is delayed, and that the delay persists after vision has recovered.[4] This is what loss of myelin predicts: signals still arrive, but late. A smaller response, by contrast, points to loss of axons. Similar tests exist for touch (somatosensory evoked potentials), for movement (motor evoked potentials) and for hearing (brainstem auditory evoked potentials).

MRI has replaced evoked potentials for most diagnostic questions, but they have found a new use in repair trials. In the ReBUILD trial, the antihistamine clemastine shortened the delay of the visual response by 1.7 milliseconds per eye in people with long-standing damage to the optic nerve, the first controlled evidence that a medicine could promote repair of myelin in MS.[5]