Changes in oxygen saturation and the retinal nerve fibre layer in patients with optic neuritis

Posted Posted in Retina

oxygen saturation, retinal nerve fibre layer, optic neuritis

2017 Nov 1. doi: 10.1111/aos.13571. [Epub ahead of print]

Changes in oxygen saturation and the retinal nerve fibre layer in patients with optic neuritis – a pilot study.

Abstract

PURPOSE:

Assessment of retinal oxygen saturation, thickness of a retinal nerve fibre layer (RNFL) and functional changes in the optic nerve during optic neuritis (ON) in patients with multiple sclerosis (MS).

METHODS:

Thirty-two patients with ON due to MS within 3 months of onset of symptoms were enrolled [22 females, 10 males, age 34 ± 9 years, median 32.5 years, 22 patients with the clinically isolated syndrome (CIS), 10 patients with relapsing-remitting from of MS (RRMS)]. All patients were examined using optical coherence tomography (OCT model 4000, Carl Zeiss Meditec, Dublin, CA, USA), automatic optical oximetry (Oxymap ehf, Reykjavik, Iceland) and using visual evoked potentials (VEP) (Metronic Keypoint® , Minneapolis, MN, USA).

RESULTS:

Arterio-venous difference (AVD) was increased in patients ON affected eye compared to patients’ unaffected eye (PUE) [34.2 ± 4.7 versus 31.3 ± 4.6, p = 0.044 (mean ± standard deviation)]. No statistically significant difference was found in vessel oxygen saturation as well as in RNFL thickness in ON affected eyes when compared to unaffected MS eyes and healthy individuals. Significantly lower optic nerve conduction velocity was found in the affected eye when compared to unaffected MS eye and healthy (p < 0.0001 for both comparisons). No correlation between oxygen saturation values and VEP was observed in patients with MS.

CONCLUSION:

The AVD in oxygen saturation is altered in patients with acute ON. In the early stage of ON, AVD could reflect inflammatory and metabolic changes in the affected eye. Therefore, oximetry could be used as another diagnostic method in MS patients in suspicion of ON. This result would be promising for future investigation in this field.

KEYWORDS oxygen saturation, retinal nerve fibre layer, optic neuritis:

multiple sclerosis; optic neuritis; optical coherence tomography; oximetry

Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial.

Posted Posted in Uncategorized

opticinumab, optic neuritis, RENEW, michael duplessie

Lancet Neurol. 2017 Mar;16(3):189-199. doi: 10.1016/S1474-4422(16)30377-5. Epub 2017 Feb 15.
Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial.
Cadavid D1, Balcer L2, Galetta S2, Aktas O3, Ziemssen T4, Vanopdenbosch L5, Frederiksen J6, Skeen M7, Jaffe GJ8, Butzkueven H9, Ziemssen F10, Massacesi L11, Chai Y12, Xu L12, Freeman S12; RENEW Study Investigators.
Author information
Abstract
BACKGROUND:
The human monoclonal antibody opicinumab (BIIB033, anti-LINGO-1) has shown remyelinating activity in preclinical studies. We therefore assessed the safety and tolerability, and efficacy of opicinumab given soon after a first acute optic neuritis episode.
METHODS:
This randomised, double-blind, placebo-controlled, phase 2 study (RENEW) was done at 33 sites in Australia, Canada, and Europe in participants (aged 18-55 years) with a first unilateral acute optic neuritis episode within 28 days from study baseline. After treatment with high-dose methylprednisolone (1 g/day, intravenously, for 3-5 days), participants were assigned with a computer-generated sequence with permuted block randomisation (1:1) using a centralised interactive voice and web response system to receive 100 mg/kg opicinumab intravenously or placebo once every 4 weeks (six doses) and followed up to week 32. All study participants and all study staff, including the central readers, were masked to treatment assignment apart from the pharmacist responsible for preparing the study treatments and the pharmacy monitor at each site. The primary endpoint was remyelination at 24 weeks, measured as recovery of affected optic nerve conduction latency using full-field visual evoked potential (FF-VEP) versus the unaffected fellow eye at baseline. Analysis was by intention-to-treat (ITT); prespecified per-protocol (PP) analyses were also done. This study is registered with ClinicalTrials.gov, number NCT01721161.
FINDINGS:
The study was done between Dec 21, 2012, and Oct 21, 2014. 82 participants were enrolled, and 41 in each group comprised the ITT population; 33 participants received opicinumab and 36 received placebo in the PP population. Adjusted mean treatment difference of opicinumab versus placebo was -3·5 ms (17·3 vs 20·8 [95% CI -10·6 to 3·7]; 17%; p=0·33) in the ITT population, and -7·6 ms in the PP population (14·7 vs 22·2 [-15·1 to 0·0]; 34%; p=0·050) at week 24 and -6·1 ms (15·1 vs 21·2 [-12·7 to 0·5]; 29%; p=0·071) in the ITT population and -9·1 ms (13·2 vs 22·4 [-16·1 to -2·1]; 41%; p=0·011) in the PP population at week 32. The overall incidence (34 [83%] of 41 in each group) and severity of adverse events (two [5%] of 41 severe adverse events with placebo vs three [7%] of 41 with opicinumab) were similar between groups and no significant effects on brain MRI measures were noted in either group (mean T2 lesion volume change, 0·05 mL [SD 0·21] for placebo vs 0·20 mL [0·52] with opicinumab; 27 [77%] of 35 participants with no change in gadolinium-enhancing [Gd+] lesion number with opicinumab vs 27 [79%] of 34 with placebo; mean 0·4 [SD 0·79 for the placebo group and 0·85 for the opicinumab group] new Gd+ lesions per participant in both groups). Treatment-related serious adverse events were reported in three (7%) of 41 participants in the opicinumab group (hypersensitivity [n=2], asymptomatic increase in transaminase concentrations [n=1]) and none of the participants in the placebo group.
INTERPRETATION:
Remyelination did not differ significantly between the opicinumab and placebo groups in the ITT population at week 24. However, results from the prespecified PP population suggest that enhancing remyelination in the human CNS with opicinumab might be possible and warrant further clinical investigation.