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Outer retinal changes following acute optic neuritis.

ABSTRACT: Retinal nerve fiber and ganglion cell+inner plexiform (GCIP) layer thinning following multiple sclerosis-related acute optic neuritis (AON) is well described. However, whether AON results in changes in the inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL) and/or photoreceptor segment (PS) layers remains undetermined.The objective of this paper is to determine if INL+OPL and/or ONL+PS changes occur following AON.Thirty-three AON patients underwent serial optical coherence tomography (OCT) and visual function testing (mean follow-up: 25 months). Longitudinal changes in retinal layer thickness were analyzed using mixed-effects linear regression.Four months following AON, the mean decrease in GCIP thickness relative to baseline was 11.4% (p < 0.001). At four months, a concomitant 3.4% increase in average ONL+PS thickness was observed (p < 0.001). The percentage decrease in GCIP thickness and increase in ONL+PS thickness were strongly correlated (r = -0.70; p < 0.001). Between months 4 to 12, ONL+PS thickness declined and, at 12 months, was no longer significantly different from baseline (mean change: 0.5%; p = 0.37). Similar, albeit less robust, changes in the INL+OPL were observed.Following AON, dynamic changes occur in the deep retinal layers, which are proportional to GCIP thinning. These novel findings help further our understanding of the biological and/or anatomical sequelae resulting from AON.

SUBMITTER: Al-Louzi OA

PROVIDER: S-EPMC4724567 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Outer retinal changes following acute optic neuritis.

Al-Louzi Omar A OA Bhargava Pavan P Newsome Scott D SD Balcer Laura J LJ Frohman Elliot M EM Crainiceanu Ciprian C Calabresi Peter A PA Saidha Shiv S

Multiple sclerosis (Houndmills, Basingstoke, England) 20150724 3

<h4>Background</h4>Retinal nerve fiber and ganglion cell+inner plexiform (GCIP) layer thinning following multiple sclerosis-related acute optic neuritis (AON) is well described. However, whether AON results in changes in the inner nuclear (INL), outer plexiform (OPL), outer nuclear (ONL) and/or photoreceptor segment (PS) layers remains undetermined.<h4>Objectives</h4>The objective of this paper is to determine if INL+OPL and/or ONL+PS changes occur following AON.<h4>Methods</h4>Thirty-three AON ...[more]

PMID: 26209589

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Project description:IMPORTANCE Retrospective studies have demonstrated disparate outcomes following acute optic neuritis in individuals of African descent compared with individuals of white race/ethnicity. However, published analyses of the prospectively collected Optic Neuritis Treatment Trial (ONTT) data identified no association between worse visual outcomes and black race/ethnicity. OBJECTIVES To investigate the associations of age, sex, and race/ethnicity with visual outcomes following acute optic neuritis through application of longitudinal data analysis techniques to the ONTT data set. DESIGN Secondary analysis of the ONTT (a prospective randomized controlled trial) data set. Our models included effects of treatment (placebo, oral prednisone, or intravenous methylprednisolone), time, and treatment × time interaction, as well as demographic covariates of age, sex, and race/ethnicity. SETTING AND PARTICIPANTS The ONTT data were collected at multiple centers in the United States. Patients of black (n = 58) and white (n = 388) race/ethnicity with acute optic neuritis who enrolled in the ONTT within 8 days of symptom onset were included in analyses. MAIN OUTCOMES AND MEASURES The contrast sensitivity and visual acuity (logMAR) in the affected eye were modeled using 2-stage mixed-effects regression techniques. All available follow-up data from baseline to 15 to 18 years were included. RESULTS The data identified no relationship of age, sex, or treatment with contrast sensitivity or visual acuity outcomes. Race/ethnicity was significantly related to contrast sensitivity (P < .001) and visual acuity (P < .001) during a 15-year period following acute optic neuritis, with black race/ethnicity being associated with worse scores for both. CONCLUSIONS AND RELEVANCE Race/ethnicity seems to be associated with contrast sensitivity and visual acuity outcomes in affected eyes following acute optic neuritis. To our knowledge, this is the largest cohort of black race/ethnicity with acute optic neuritis to be studied and represents the first evidence from a prospectively collected data set to support a hypothesis of race/ethnicity-dependent visual outcomes of acute optic neuritis.

Project description:Importance:Clinical outcome in multiple sclerosis was suggested to be driven by not only remyelination but also adaptive reorganization. This mechanism needs to be further understood. Objective:To explore anatomical and functional visual networks in patients with optic neuritis (ON) to assess the relative weight of each connectivity modality to expedite visual recovery. Design, Setting, and Participants:Between March 11, 2011, and May 26, 2014, 39 patients with either clinically isolated syndrome (CIS) ON (n = 18) or other CIS (non-ON) (n = 21) were recruited 1 to 28 months following an initial clinical event. These patients enrolled in an ongoing prospective cohort study (107 participants at the time of this present study) about the disease course of CIS and multiple sclerosis. Inclusion criteria were an age of 18 to 65 years, the suggestive clinical and paraclinical diagnosis of CIS or multiple sclerosis after relevant differential diagnoses have been ruled out, the existence of complete imaging data, and no ocular comorbidities. Anatomical connectivity was evaluated by diffusion tensor imaging, and functional connectivity was evaluated by resting-state functional magnetic resonance imaging. The visual pathways, including optic tracts, optic radiations, and splenial fibers, were delineated, and the resting-state visual networks were detected. Data analysis took place from September 1, 2015, to December 1, 2015. Main Outcomes and Measures:Connectivity changes were quantified and compared to determine the association of ON with the visual network. Results:This study included 18 patients with CIS ON, 11 (61%) of whom were women with a mean (SD) age of 32.83 (8.53) years, and 21 patients with CIS non-ON (11 [52%] of whom were women with a mean [SD] age of 30.86 [7.54] years). With the use of diffusion tensor imaging, reduced diffusivity (mean [SD] fractional anisotropy, 0.35 [0.03] vs 0.38 [0.03]; P < .01) was evident along the optic tracts of patients with ON, suggesting the extension of axonal injury from the damaged optic nerve. Neither the optic radiations nor the splenial fibers showed evidence of loss of integrity. Yet, in the presence of an intact postgeniculate anatomical network, the functional connectivity within the visual network was higher in the ON cohort. Functional connectivity observed in cortical motion-related areas was inversely correlated with the visual evoked potential-measured conduction velocity (r = -0.59; P < .05). Conclusions and Relevance:In this cohort, local optic nerve demyelinating damage does not affect distant wiring, but even in the presence of an intact anatomical network, functional modification may occur. These functional network changes may be part of the recovery process, but further research is needed to elucidate this process.

Project description:Acute optic neuritis treatment lacks standardized protocols. The value of oral prednisone taper (OPT) following intravenous methylprednisolone (IVMP) on visual outcome parameters in optic neuritis (ON) has never been explored. In the present retrospective study, we investigated whether OPT after IVMP affects the structural and functional visual outcomes of inaugural clinically isolated syndrome (CIS)- or multiple sclerosis (MS)-ON. Adult patients with acute, inaugural, unilateral CIS- or MS-ON, treated with IVMP in Germany and Israel were stratified into patients treated with IVMP alone-versus IVMP and OPT. Inclusion criteria were age ≥18, CIS or MS diagnosis according to McDonald criteria 2017, available visual acuity (VA) at nadir before treatment initiation and at follow-up ≥5 months, as well as a spectral domain optic coherence tomography (OCT) data scan at follow-up. Exclusion criteria included recurrent ON, concomitant ophthalmological comorbidities, optical coherence tomography (OCT) of insufficient quality and ON-related escalation therapy after IVMP. The structural outcome was defined as the average retinal nerve fiber layer (RNFL) difference between the ON-affected and the unaffected eye, while the functional outcome was defined as the final high-contrast best-corrected VA (HC-BCVA) at follow-up compared to nadir. The comparative analysis was performed using linear regression analysis, adjusted for sex, age, and days-to-treatment. Fifty-one patients met the inclusion criteria (25% male). The mean age was 33.9 (±10.23) years. Twenty-six patients (51%) received OPT following IVMP. There was no difference in nadir HC-BCVA between the groups (0.39 No OPT; 0.49 With OPT, P = 0.36). Adjusted linear regression analysis did not indicate an influence of OPT on RNFL thickness or on HC-BCVA (beta coefficient for RNFL difference in percentages: 0.51, 95%-CI: [-4.58, 5.59], beta coefficient for logMAR: 0.11, 95%; CI [-0.12, 0.35] at follow-up. In conclusion, the addition of OPT to IVMP did not affect RNFL thickness or the final VA in a retrospective cohort of 51 patients with inaugural acute CIS- or MS-ON. The results of this exploratory study are currently being re-examined in a large-scale, demographically diverse, prospective study.

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Outer retinal changes following acute optic neuritis.

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Outer retinal changes following acute optic neuritis.

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