Retinal Nerve Fiber Layer Atrophy Research Articles

Differences in Retinal Nerve Fiber Layer Atrophy Between Multiple Sclerosis Subtypes: A Tunisian Cohort

Differences in Retinal Nerve Fiber Layer Atrophy Between Multiple Sclerosis Subtypes: A Tunisian Cohort

Treatment With Erythropoietin for Patients With Optic Neuritis: Long-term Follow-up.

Erythropoietin (EPO) is a candidate neuroprotective drug. We assessed its long-term safety and efficacy as an adjunct to methylprednisolone in patients with optic neuritis and focused on conversions to multiple sclerosis (MS). The TONE trial randomized 108 patients with acute optic neuritis but without previously known MS to either 33,000 IU EPO or placebo in conjunction with 1,000 mg methylprednisolone daily for 3 days. After reaching the primary end point at 6 months, we conducted an open-label follow-up 2 years after randomization. The follow-up was attended by 83 of 103 initially analyzed patients (81%). There were no previously unreported adverse events. The adjusted treatment difference of peripapillary retinal nerve fiber layer atrophy in relation to the fellow eye at baseline was 1.27 µm (95% CI -6.45 to 8.98, p = 0.74). The adjusted treatment difference in low-contrast letter acuity was 2.87 on the 2.5% Sloan chart score (95% CI -7.92 to 13.65). Vision-related quality of life was similar in both treatment arms (National Eye Institute Visual Functioning Questionnaire median score [IQR]: 94.0 [88.0 to 96.9] in the EPO and 93.4 [89.5 to 97.4] in the placebo group). The rate of multiple sclerosis-free survival was 38% in the placebo and 53% in the EPO group (hazard ratio: 1.67, 95% CI 0.96 to 2.88, p = 0.068). In line with the results at 6 months, we found neither structural nor functional benefits in the visual system of patients with optic neuritis as a clinically isolated syndrome, 2 years after EPO administration. Although there were fewer early conversions to MS in the EPO group, the difference across the 2-year window was not statistically significant. This study provides Class II evidence that for patients with acute optic neuritis, EPO as an adjunct to methylprednisolone is well tolerated and does not improve long-term visual outcomes. The trial was preregistered before commencement at clinicaltrials.gov (NCT01962571).

Effect of Vascular Comorbidity on Visual and Disability Outcomes in a Secondary Progressive Multiple Sclerosis Clinical Trial Cohort.

Vascular comorbidity (VC) is associated with multiple sclerosis (MS) disease progression and visual dysfunction. The longitudinal effect of VC in people with secondary progressive MS (SPMS) is unclear. This study explored the impact of VC on standard clinical, MRI, and visual outcomes in people with SPMS enrolled in a clinical trial. Data were extracted from a 2-year randomized controlled trial (N = 51) testing the supplement lipoic acid in people with SPMS who underwent annual Expanded Disability Status Scales, Timed 25-Foot Walk tests, MRIs, visual acuity testing, and retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GCIPL) thicknesses per optical coherence tomography (OCT). Post hoc linear mixed-effects regression analysis compared baseline and annualized outcomes between participants without VC (VC-) and with 1 or more VCs (VC+) (hypertension, dyslipidemia, obesity, diabetes, peripheral or cardiovascular disease, tobacco use). The VC- (n = 19) and VC+ (n = 28) participants were similar in age, sex, and MS disease duration and had comparable MS disability, mobility, and brain atrophy at baseline and throughout the 2-year parent study. The VC+ participants had worse baseline visual acuity than those in the VC- group by 0.13 logMAR (P = .041). No significant differences were detected in RNFL or GCIPL baseline thickness or atrophy between groups. In an SPMS cohort, VC had an inconsistent effect on standard clinical, MRI, and exploratory OCT outcomes, suggesting that the effect of VC may not be evident in smaller cohort studies. Using a more refined definition of VC in future, adequately powered investigations may help effectively elucidate and account for the interaction between vascular risk burden and MS disability.

Upregulated Retinal Neurofilament Expression in Experimental Optic Neuritis

ABSTRACT In optic neuritis (ON), transient thickening of the macular retinal nerve fibre layer (RNFL) can be observed. This optical coherence tomography-based observation is not understood. The axonal diameter correlates with the neurofilament (Nf) protein content, but there are no data on the retinal tissue concentration of Nfs. The myelin-oligodendrocyte-glycoprotein (MOG) induced experimental autoimmune encephalomyelitis (EAE) model was used to investigate the retinas of Brown Norway rats with (i) visual evoked potentials (VEP) confirmed ON, (ii) VEP confirmed absence of ON and (iii) control animals. Twenty retinas were collected from MOG-EAE and control rats 27 days after immunisation. Retinal tissue Nf concentrations per total protein (μg/mg) were significantly higher in MOG-EAE rats with ON (median 4.29, interquartile range [IQR] 3.41–5.97) compared with MOG-EAE rats without ON (1.14, IQR 1.10–1.67) or control rats (0.93, IQR 0.45–4.00). The data suggest that up-regulation of Nf expression in the retinal ganglion cells precedes development of RNFL atrophy and plausibly explains the transient increase of axonal diameter and RNFL thickening.

Cognitive Decline in Multiple Sclerosis Is Related to the Progression of Retinal Atrophy and Presence of Oligoclonal Bands: A 5-Year Follow-Up Study.

Background: Brain atrophy, which is associated with cognitive impairment and retinal nerve fiber layer (RNFL) atrophy, is the main biomarker of neurodegeneration in multiple sclerosis (MS). However, data on the relationship between inflammatory markers, such as oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF), and cognition, RNFL atrophy, and brain atrophy are scarce. The aim of this study was to assess the influence of RNFL thickness, brain atrophy markers, intrathecal OCBs, and the immunoglobulin G (IgG) index on cognitive decline over a 5-year period in patients with MS.Methods: This prospective, single-center, observational cohort study included 49 patients with relapsing MS followed up over 5 years. At baseline, the patients underwent brain magnetic resonance imaging (MRI). Cognitive evaluation was performed using the Brief International Cognitive Assessment for MS (BICAMS), and RNFL thickness was assessed using optical coherence tomography (OCT). OCBs and IgG levels in the CSF were evaluated at baseline. The BICAMS, OCT, and MRI findings were re-evaluated after 5 years.Results: A significant reduction in information processing speed, visual learning, temporal RNFL thickness, the Huckman index, and third ventricle mean diameter was found in all 49 patients with relapsing MS over the observation period (p < 0.05). Of the patients, 63.3% had positive OCBs and 59.2% had elevated IgG indices. The atrophy of the temporal segment and papillomacular bundle and the presence of OCBs were significantly related to a decline in information processing speed in these patients (p < 0.05). However, brain atrophy markers were not found to be significant on the general linear models.Conclusions: RNFL atrophy and the presence of OCBs were related to cognitive decline in patients with MS over a 5-year follow-up period, thereby suggesting their utility as potential biomarkers of cognitive decline in MS.

Axonal Degeneration Independent of Inflammatory Activity: Is It More Intense in the Early Stages of Relapsing-Remitting Multiple Sclerosis Disease?

Background: This study aimed to investigate whether there are differences in the axonal degeneration rate between patients in the early years of relapsing-remitting multiple sclerosis (RRMS) disease and RRMS patients in their later years. Methods: The early-stage RRMS patients (EMS) group had 65 patients whose duration of disease was within 3 years from the date of the first attack. The late-stage RRMS patients (LMS) group had 69 patients whose duration of disease was within the range of 3–10 years from the date of the first attack. In addition, a control group was composed of 32 healthy subjects. Peripapillary retinal nerve fiber layer (RNFL) thickness was monitored with spectral-domain OCT in all included patients for approximately 3 years. Results: The annual RNFL atrophy rate (aRNFLr) in the EMS group was −1.246 ± 0.778 μm/year, the aRNFLr in the LMS group was −0.898 ± 0.536 μm/year, and the aRNFLr was −0.234 ± 0.154 μm/year in the control group (p < 0.001). The aRNFLr in the EMS group was significantly higher than the aRNFLr in the LMS group (p = 0.01). The aRNFLr was not associated with MRI activity or the condition of having an attack. There was a correlation between Expanded Disability Status Scale (EDSS) progression and aRNFLr in both the EMS and LMS patient groups (r = −0.471, p < 0.001, and r = −0.567, p < 0.001, respectively). Conclusion: The axonal degeneration rate is faster in RRMS patients in the first years of the disease than in later years. In addition, axonal degeneration occurs independently of inflammatory activity. Axonal degeneration is correlated with disability progression, but not with inflammatory findings, such as clinical episodes and MRI activity.

Visual field loss and structure–function relationships in optic neuritis associated with myelin oligodendrocyte glycoprotein antibody

Background: A paradoxical discrepancy between severe peripapillary retinal nerve fiber layer (pRNFL) atrophy and good visual outcome had been reported in patients with myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated optic neuritis (ON). However, only visual acuity (VA) was assessed. Objectives: To study visual field (VF) outcomes of patients with MOG-IgG-associated ON and evaluate the correlation between functional eye outcome and retinal structural changes assessed by optical coherence tomography. Methods: The records of 32 patients with MOG-IgG-associated ON who underwent ophthalmological examination at least 12 months after ON onset were reviewed. Degree of VF disability was determined by mean deviation (MD). Results: At final assessment (median, 35 months), 4.2% of 48 affected eyes (AE) had VA ⩽ 0.1, 40% had abnormal MD, and among AE with final VA ⩾ 1.0, 31% had mild to moderate damage. Thinning of the inner retinal layers was significantly correlated with MD impairment. Analysis demonstrated a threshold of pRNFL thickness (50 µm), below which MD was significantly worse (mean, −2.27 dB vs −17.72 dB; p = 0.0003). ON relapse was significantly associated with poor visual outcome assessed by MD. Conclusion: Functional impairment measured with VF is not rare, and MD assessment better reflects actual structural damage.

Treatment of Optic Neuritis With Erythropoietin (TONE): A Randomized, Double-Blind, Placebo-Controlled Study

Background: The human cytokine erythropoietin (EPO) conveys neuroprotection in preclinical models and has shown ambiguous results in phase 2 clinical trials in optic neuritis. We assessed the efficacy and safety of EPO in optic neuritis as a clinically isolated syndrome in a sufficiently powered RCT. Methods: This randomized, placebo-controlled, double-blind phase 3 trial conducted at 12 German tertiary care centres included participants aged 18-50 years with an acute presentation of unilateral optic neuritis within 10 days, visual acuity ≤ 0·5 and without previously known multiple sclerosis. Participants were randomly assigned (1:1) to receive either 33.000 IU erythropoietin or placebo intravenously for three days as an adjunct to high-dose methylprednisolone (1000 mg/day). Block Randomisation was performed with randomly varying block sizes, stratified by study site and distributed using sealed envelopes. All trial participants and all study staff were masked from treatment assignment with the exception of the trial pharmacist. The first primary outcome was the amount of retinal nerve fibre layer (RNFL) atrophy, measured by optic coherence tomography (OCT) as the difference in RNFL thickness between the affected eye at week 26 and the unaffected eye at baseline. The second primary outcome was low contrast visual acuity at week 26, measured as the 2·5% Sloan chart score of the affected eye. Analysis was performed in a set of all randomised participants for whom treatment was started and at least one follow-up OCT measurement was available. Safety was analysed in all patients who received at least one dose of the trial medication. Findings: The study enrolled 108 participants between November 25 th , 2014 and October 9 th , 2017, 55 of which were assigned to EPO and 53 to placebo. Five patients were excluded from the primary analysis due to screening failure, revised diagnosis or loss to follow-up, yielding a full analysis set of 52 EPO and 51 placebo recipients. The adjusted mean treatment difference of EPO versus placebo was 1·02 µm of RNFL atrophy (95% CI -5·51 to 7·55; p=0·76; unadjusted 15·9 vs 14·7 µm) and -4·03 (-13·6 to 5·01; p=0·38) on the letter score for low contrast visual acuity (unadjusted 49·06 vs 49·60). One patient in the EPO group developed a sinus venous thrombosis which was treated with anticoagulants and resolved without sequelae. Interpretation: EPO conveyed neither functional nor structural neuroprotection in the visual pathways after optic neuritis. Trial Registration: This trial is registered with ClinicalTrials.gov (NCT01962571). Funding Statement: German Ministry of Health and Science (BMBF), Clinical trials programme. Declaration of Interests: WL reports grants from the German Federal Ministry for Education and Research (BMBF) and the German Research Foundation (DFG). He received speakers’ honoraria from and worked on advisory boards for Alcon, Allergan, Santhera, Boehringer Ingelheim, and Merz Pharma. SK has received a doctoral fellowship with funding from the University of Freiburg, Faculty of Medicine and the Else Kroner-Fresenius foundation. GI has received funding from Novartis and Janssen Pharmaceutica. BG and FB have nothing to report. MV has worked on an advisory board for Roche Pharma. SH has received funding from the DFG, the German Federal Institute for Sport Science and the German Ophthalmological Society. PA reports reports grants, personal fees, and non-financial support from Allergan, Biogen, Celgene, Ipsen, Merck, Merz Pharmaceuticals, Novartis, Roche, and Teva outside the submitted work. JU has received a doctoral fellowship with funding from the Ministry of Science, Research and Arts Baden-Wuerttemberg as part of the HAW-Prom program. She received a speakers’ honorary from AMO Ireland (affiliated to Johnson & Johnson Vision) and is co-inventor of patents/patent applications with the numbers 10 2017 126 741, WO 2020/089284 A1 and 20 174 551.0. MW is a managing partner of Blickshift GmbH and coinventor of patent applications WO 2020/089284 A1 and 20 174 551.0. MH reports grants from Bristol-Myers Squibb and speaker’s honoraria from Amgen, Baxter Deutschland, CSL Behring, Biotest Pharma, Fresenius Kabi, Leo Pharma, Merck Serono, Novartis Pharma, Pfizer, Roche Pharma, and Sun Pharmaceuticals Industries. SW has served as a consultant for Bayer, Novartis, Chengdu Kanghong Biotech, Zeiss, and Roche and has received grant support from Zeiss and Heidelberg Engineering. RD was funded by the BMBF, the DFG, and the Hertie Foundation. Ethics Approval Statement: The study protocol was approved by the institutional review boards and ethics committees of each participating site under the conduct of the ethics committee of the University of Freiburg, Germany.

Optic nerve head width and retinal nerve fiber layer changes are proper indexes for validating the successful induction of experimental anterior ischemic optic neuropathy

Reproducible skills are essential for successful induction of a rat model of anterior ischemic optic neuropathy (rAION). We established an in vivo validation index by measuring the natural course of optic nerve head (ONH) width and retinal nerve fiber layer (RNFL) thickness in the rAION model using optical coherence tomography (OCT). The rAION model was induced by photodynamic operations. We measured the ONH width, RNFL, Inner Plexiform layer (IPL) and Ganglion cell complex (GCC) thickness in the acute stage (<3 days), subacute stage (day-7 to day-14) and later stage (day-14 to day-28) post-infarct by OCT. Retinal layers were measured by hematoxylin and eosin stain (HE) to confirm the OCT findings. The RGCs survival rate was determined by retrograde Fluoro-gold labeling, and the visual function was assessed with flash visual-evoked potentials (FVEPs) 4 weeks post-infarct. We observed significant thinning in GCC, IPL, and RNFL at day-14 and day-28 but only RNFL showed significant thinning between day-14 and day-28. The ONH showed significant swelling in the acute stage which correlated at a greater extent with RNFL than GCC and IPL. Further RNFL correlated at a greater extent at with GCC than IPL. HE-stained retina cross sections also showed IPL and RNFL thinning, which further confirmed our OCT findings. The RGC density and P1-N2 amplitude were significantly reduced in rAION. Our data suggest that Swelling, reduction of swelling, and atrophy of RNFL in acute, sub-acute, and later stage, respectively and ONH swelling in the acute stage are essential events for confirming the successful induction of rAION.

Peripapillary and parafoveal vascular network assessment by optical coherence tomography angiography in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders

Background/aimsCurrent understanding of the alterations in the retinal vascular network in neuromyelitis optica spectrum disorders (NMOSDs) is limited. We aim to assess the peripapillary and parafoveal vessel density in aquaporin-4...

Optical Coherence Tomography Measurement and Visual Outcome in Acute Central Retinal Artery Occlusion.

PurposeThis study investigated visual acuity (VA) values and differences depending on optical coherence tomography (OCT) findings in patients with acute central retinal artery occlusion (CRAO).MethodsA retrospective chart review was performed on patients with acute CRAO who underwent macular and disc OCT. We evaluated changes in macular thickness and retinal nerve fiber layer (RNFL) thickness after acute CRAO onset based on OCT. We also determined the association of thickness changes with VA improvement.ResultsThis study involved both eyes in a total of 12 patients with acute CRAO. A significant increase was observed in foveal (1 mm) thickness (p = 0.002), parafoveal (3 mm) thickness (p = 0.002), and peripapillary RNFL thickness (p = 0.005) in affected eyes with CRAO, but not in central foveal thickness (p = 0.266). A significant small difference in both eyes (affected eye – fellow eye) was shown in foveal (1 mm) and mean parafoveal (3 mm) thickness in the improved VA group (p = 0.008 and p = 0.004, respectively), but not in central foveal or peripapillary RNFL thickness (both p = 0.283).ConclusionsBoth macular and RNFL thickness increased in patients with acute CRAO. RNFL thickness decreased over time with progression of RNFL atrophy. Less macular damage caused by acute CRAO could be predicted by a small difference in macular thickness between eyes (affected eye – fellow eye). In such cases, patients had a greater chance of VA improvement.

Longitudinal optical coherence tomography study of optic atrophy in secondary progressive multiple sclerosis: Results from a clinical trial cohort

Background: Limited prospective information exists regarding spectral-domain optical coherence tomography (SD-OCT) in secondary progressive multiple sclerosis (SPMS). Objective: Document cross-sectional and longitudinal retinal nerve fiber layer (RNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) features of an SPMS clinical trial cohort. Methods: Prospective, observational study using a 2-year randomized placebo-controlled SPMS trial cohort with yearly SD-OCT testing. Post hoc analysis determined influences of optic neuritis (ON), disease duration, and baseline SD-OCT on annualized atrophy rates and on correlations between OCT and brain atrophy. Results: Mean RNFL and GCIPL values of patients (n = 47, mean age = 59 years, mean disease duration = 30 years) were significantly lower among eyes with prior ON than those without (no history of ON (NON)). Annualized RNFL (−0.31 µm/year) and GCIPL (−0.29 µm/year) atrophy rates did not differ between ON and NON eyes. Baseline RNFL thickness >75 µm was associated with greater annualized RNFL atrophy (−0.85 µm/year). Neither RNFL nor GCIPL atrophy correlated with whole-brain atrophy. Conclusion: This study suggests that eyes with and without ON history may be pooled for atrophy analysis in SPMS clinical trials using SD-OCT. Low baseline RNFL, small retinal atrophy rates, and lack of correlation with whole-brain atrophy in this population are important trial design considerations.

OCT Angiography of the Peripapillary Retina in Primary Open-Angle Glaucoma.

The purpose of this study was to investigate the topographic relationship between the decreased parapapillary retinal microvasculature as assessed by optical coherence tomography angiography (OCTA) and retinal nerve fiber layer (RNFL) defect in eyes with primary open-angle glaucoma (POAG) and a localized RNFL defect. The peripapillary retinal circulation was evaluated using the OCTA centered on the optic nerve head in 98 POAG eyes having a localized RNFL defect and 45 healthy control eyes. A vascular impairment (VI) was identified in OCTA by the presence of a sign indicating decreased microvasculature. The frequencies of VI were compared between the POAG and control groups, and the topographic correlation between the VI and the RNFL defect identified in red-free fundus photographs was determined in the POAG group. The VI was observed as an area of decreased density of the microvascular network of the retina in 100% of the POAG eyes. The VI exactly coincided with the RNFL defect evident in red-free fundus photographs in terms of both the location and extent (Pearson's correlation coefficient = 0.997 and 0.988, respectively, all P < 0.001). None of the control eyes exhibited VI in OCTA. Decreased parapapillary microvasculature of the retina determined by OCTA was found at the location of RNFL defect in POAG patients. This finding suggests that the decreased retinal microvasculature is likely secondary loss or closure of capillaries at the area of glaucomatous RNFL atrophy.

Retinal nerve fiber layer atrophy in patients with multiple sclerosis: Longitudinal 5 years study

PurposeTo evaluate changes in the retinal nerve fiber layer (RNFL) thicknesses in multilple sclerosis (MS) patients compared with healthy subjects during 5 years of follow up. To compare ability of optical coherence tomography (OCT) and visual field test to detect axonal damage.MethodsFifty eyes of 50 MS patients and 50 eyes of 50 healthy controls were included. All of them underwent measurements of best corrected visual acuity (BCVA) refractive defect, color vision, visual field, and OCT (Spectralis OCT). All of them were annual re‐evaluated during 5 years. Change in both groups (MS patients and healthy controls) were evaluated and compared using paired T Student′s test.ResultsWe found decrease in all RNFL thicknesses during the 5 years follow‐up in both groups (patients and controls), and the changes were significant higher in MS group (T Student′s, p ≤ 0.05). No differences were found between patients and controls in visual functional tests (BCVA, color vision test and visual field). Higher change was found in inferior quadrant (113.67 in baseline and 105.39 μm in 5 years visit in MS group, p &lt; 0.001). Correlations between structural and functional tests were found, but not between the changes in both tests during the 5 years follow up.ConclusionsMS progression causes axonal damage that can be detected by OCT but not by visual functional tests.

Comparison of the retinal measurements of standard and neurological SD‐OCT applications in MS patients

PurposeIn multiple sclerosis (MS), spectral domain optical coherence tomography (SD‐OCT) provides a tool to evaluate structural retinal changes related to MS. Recently, an application dedicated to visualize and quantify changes in MS and other neurodegenerative diseases became commercially available. Unlike the standard SD‐OCT, it is not yet widespread in eye clinics in Finland. Therefore, aim of the present study was determine if correlation exists in the retinal measurements between this and standard SD‐OCT application, using scan pattern presets feasible in monitoring of MS.MethodsSeven patients (mean age 48.2 ± 12.8 years) with previously diagnosed MS were examined in both eyes with Spectralis SD‐OCT (Heidelberg, Germany) in Kuopio University Hospital, Finland. Retinal nerve fibre layer (RNFL) thickness scans around the peripapillary retina (PPR) were performed with the Nsite Analytics and the standard glaucoma application (Heidelberg). Volumes of the retina and its layers in the 9 macular sectors, as defined by the Early Treatment Diabetic Retinopathy Study (ETDRS), were measured by Heyex Viewing Module software with automated retinal layer segmentation (Heidelberg).ResultsCorrelations between the measurements of the Nsite Analytics and the standard application were strong (r &gt; 0.9; p &lt; 0.01) in PPR RNFL thickness and in total macular retinal volume. In part, correlations of retinal layer volumes were weaker. Both applications interpreted the degree of PPR RNFL atrophy in a comparable manner (κ &gt; 0.7; p &lt; 0.01), except the temporal superior sector.ConclusionsAs an accessible alternative, the standard SD‐OCT can be used for measuring retinal changes in MS patients. However, an application actually designed for neurological diseases provides tools to visualize these changes and to evaluate the degree of the thickening of PPR RNFL above normal limits.

Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD.

We characterized a unique group of patients with neuromyelitis optica spectrum disorder (NMOSD) who carried autoantibodies of aquaporin-4 (AQP4) and myelin-oligodendrocyte glycoprotein (MOG). Among the 125 NMOSD patients, 10 (8.0%) were AQP4- and MOG-ab double positive, and 14 (11.2%) were MOG-ab single positive. The double-positive patients had a multiphase disease course with a high annual relapse rate (P=0.0431), and severe residual disability (P<0.0001). Of the double-positive patients, 70% had MS-like brain lesions, more severe edematous, multifocal regions on spinal magnetic resonance imaging (MRI), pronounced decreases of retinal nerve fiber layer thickness and atrophy of optic nerves. In contrast, patients with only MOG-ab had a higher ratio of monophasic disease course and mild residual disability. Spinal cord MRI illustrated multifocal cord lesions with mild edema, and brain MRIs showed more lesions around lateral ventricles. NMOSD patients carrying both autoantibodies to AQP4 and MOG existed and exhibited combined features of prototypic NMO and relapsing-remitting form of MS, whereas NMOSD with antibodies to MOG only exhibited an “intermediate” phenotype between NMOSD and MS. Our study suggests that antibodies against MOG might be pathogenic in NMOSD patients and that determination of anti-MOG antibodies maybe instructive for management of NMOSD patients.

Update on the Medical Treatment of Primary Open-Angle Glaucoma.

Glaucoma comprises a group of progressive, neurodegenerative disorders characterized by retinal ganglion cell death and nerve fiber layer atrophy. Several randomized controlled trials have consistently demonstrated the efficacy of intraocular pressure lowering to slow or halt the measurable progression of the disease. Medical therapy, in places where it is easily accessible, is often the primary method to lower intraocular pressure. We review the medical options currently available and possible future options currently in development. The 5 contemporary classes of topical agents in use include prostaglandin analogs, beta blockers, carbonic anhydrase inhibitors, alpha agonists, and cholinergics. In addition, several fixed combination agents are commercially available. Agents from each of these classes have unique mechanisms of action, adverse effects, and other characteristics that impact how they are used in clinical practice. Despite the plethora of medical options available, there are limitations to topical ophthalmic therapy such as the high rate of noncompliance and local and systemic adverse effects. Alternate and sustained drug delivery models, such as injectable agents and punctal plug delivery systems, may in the future alleviate some such concerns and lead to increased efficacy of treatment while minimizing adverse effects.

7.: Antibodies targeting myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis

Autoantibodies such as those targeting aquaporin-4 are important biomarkers in central nervous system demyelination. We examined a cohort of patients with aquaporin-4 antibody seronegative neuromyelitis optica spectrum disorder (NMOSD) for serum antibodies against the autoantigen myelin oligodendrocyte glycoprotein (MOG). We performed a flow cytometry cell-based assay using live human embryonic kidney 293 cells lentivirus-transduced to express full-length surface MOG. We tested the serum of 23 adult patients with aquaporin-4 antibody seronegative NMOSD, including bilateral and recurrent optic neuritis (BON; n=11), longitudinally extensive transverse myelitis (LETM; n=10), and sequential BON and LETM (n=2), as well as patients with multiple sclerosis (MS; n=76), and controls (n=52), for the presence of MOG antibodies (MOG-Abs). MOG-Abs were detected in 9/23 patients with aquaporin-4 antibody seronegative NMOSD compared to 1/76 MS patients and 0/52 controls (<i>p</i><0.001). MOG-Abs were detected in 8/11 BON, 0/10 LETM, and 1/2 sequential BON and LETM patients. MOG-Ab positive patients were significantly more likely to relapse, have a rapid response to steroid therapy, and relapse on steroid cessation than MOG-Ab negative patients (<i>p</i><0.05). Serial samples showed an association of MOG-Abs with relapse. While 8/9 MOG-Ab positive patients had a favourable visual outcome, one experienced sustained visual impairment, three had retinal nerve fiber layer atrophy on follow-up, and one had residual spinal disability. Antibodies to MOG have a strong association with bilateral and recurrent optic neuritis, and may be a clinical biomarker. MOG-Abs associated BON is a relapsing disorder which is frequently steroid responsive and often steroid dependent. Failure of early recognition and institution of immunotherapy may be associated with sustained impairment.

Neutralizing IL-17 protects the optic nerve from autoimmune pathology and prevents retinal nerve fiber layer atrophy during experimental autoimmune encephalomyelitis

Optic neuritis is a common inflammatory manifestation of multiple sclerosis (MS). In experimental autoimmune encephalomyelitis (EAE), the optic nerve is affected as well. Here, we investigated whether autoimmune inflammation in the optic nerve is distinct from inflammation in other parts of the central nervous system (CNS). In our study, inflammatory infiltrates in the optic nerve and the brain were characterized by a high fraction of Ly6G+ granulocytes whereas in the spinal cord, macrophage infiltrates were predominant. At the peak of disease, IL-17 mRNA abundance was highest in the optic nerve as compared with other parts of the CNS. The ratio of IL-17 vs IFN-γ producing CD4+ T cells was higher in the optic nerve and brain than in the spinal cord and more effector CD4+ T cells were committed to the Th17 transcriptional program in the optic nerve than in the spinal cord. IL-17 producing γδ T cells but rather not Ly6G+ granulocytes themselves contributed to IL-17 production. Optical coherence tomography (OCT) studies on murine eyes revealed a decline in thickness of the retinal nerve fiber layer (RNFL) and the common layer of ganglion cells and inner plexiform layer (GCL+) after the recovery from motor symptoms indicating that autoimmune inflammation induced a significant atrophy of optic nerve fibers during EAE. Neutralization of IL-17 by treatment with anti-IL-17 antibodies reduced but did not abrogate motor symptoms of EAE. However, RNFL and GCL+ atrophy were completely prevented by blocking IL-17. Thus, the optic nerve compartment is particularly prone to support IL-17 mediated inflammatory responses during CNS autoimmunity and structural integrity of the retina can be preserved by neutralizing IL-17.

Reliability and validity of Cirrus and Spectralis optical coherence tomography for detecting retinal atrophy in Alzheimer’s disease

To evaluate and compare the ability of two Fourier-domain optical coherence tomography (OCT) devices to detect retinal and retinal nerve fibre layer (RNFL) atrophy in patients with Alzheimer's disease (AD) compared with healthy subjects; to test the intra-session reliability of two OCT devices in AD patients and healthy subjects. AD patients (n=75) and age-matched healthy subjects (n=75) underwent three Macular Cube 200 × 200 protocols using the Cirrus and Spectralis OCT devices and three 360° circular scans centred on the optic disc using the Cirrus OCT device, the classic glaucoma application, and the new Nsite Axonal Analytics application of the Spectralis OCT instrument. Differences between healthy and AD eyes were compared, and measurements provided by each OCT protocol were compared. Reliability was measured using intraclass correlation coefficients and coefficients of variation. Correlations between OCT measurements and disease duration and severity were also analysed. Retinal thinning was observed in AD eyes in all areas except the fovea using both OCT devices. RNFL atrophy was detected in AD eyes with all three protocols, but the Nsite Axonal application was the most sensitive. Measurements by the two OCT devices were correlated, but differed significantly. Reliability was good using all protocols, but better with the glaucoma application of Spectralis. Mean RNFL thickness provided by the Nsite Axonal application correlated with disease duration. Fourier-domain OCT is a valid and reliable technique for detecting subclinical RNFL and retinal atrophy in AD, especially using the Nsite Axonal application. RNFL thickness decreased with disease duration.