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Background Several studies have suggested that the retina structure is affected in schizophrenia spectrum disorders (SSD). We aimed to investigate the location and size of the potential differences between patients and healthy controls (HC) in several thickness and volume measures across the retina Study Design We included cross-sectional studies comparing peripapillary retinal nerve fiber layer (pRNFL) thickness, macular volume, macular thickness (MT), foveal thickness, ganglion cell and inner plexiform layer thickness (GCL+IPL), cup volume, and cup/disc ratio (C/D) in the right and/or left eyes and/or the pRNFL and MT quadrants between patients with SSD and HC. Search databases were MEDLINE, Web of Science, PsycINFO, Cochrane Central, and medrxiv.org. Risk of bias was assessed with the Newcastle-Ottawa Scale. Standardized mean differences (SMD), subgroup analysis, and meta-regression with several variables were computed using the dmetar package in R. PROSPERO: CRD42021287873. Study Results Data from 22 reports (942 patients, 742 HC) were included. We found a retinal thinning in pRNFL (−0.30; 95% CI: −0.46, −0.14), macula (−0.37; 95% CI: −0.61, −0.13), and GCL+IPL (−0.33; 95% CI: −0.57, −0.10). The retinal thinning was especially pronounced in the superior and inferior quadrants of the inner ring of the macula. We also observed a decrease of macular volume (−0.44; 95% CI: −0.68, −0.20) and an increase in C/D ratio (0.35; 95% CI: 0.03, 0.67). Conclusions Current evidence demonstrates retinal thinning in SSD, affecting both axonal and cellular structures, specially focused in the inner ring of the macula.

Macular oedema is a rare complication of fingolimod treatment. It usually presents within 3–4 months, but occasionally presents later. It can resolve without treatment despite continuation of fingolimod treatment. Herein we report a case of very late onset macular oedema in a 49-year-old woman with multiple sclerosis treated with fingolimod for 7 years. The patient presented with blurred vision in both eyes with visual acuities of 20/32 in her right eye and 20/25 in her left eye. She had macular oedema, that without discontinuing fingolimod treatment, resolved after 1 month.

Understanding of the role of focal inflammation, a treatable feature, on neuro-axonal injury, is paramount to optimize neuroprotective strategy in MS. To quantify the impact of focal inflammatory activity on the rate of neuro-axonal injury over the MS course. We quantified the annualized rates of change in peripapillary retinal nerve fiber layer, ganglion cell plus inner plexiform layer (GCIPL), whole-brain, gray matter and thalamic volumes in patients with and without focal inflammatory activity in 161 patients followed over 5 years. We used mixed models including focal inflammatory activity (the presence of at least one relapse or a new/enlarging T2-FLAIR or gadolinium- enhancing lesion), and its interaction with time adjusted by age, sex, use of disease-modifying therapies and steroids, and prior optic neuritis. The increased rate of neuro-axonal injury during the first five years after onset was more prominent among active patients, as reflected by the changes in GCIPL thickness (p = 0.02), whole brain (p = 0.002) and thalamic volumes (p

Purpose Raman spectroscopy allows molecular changes to be quantified in vivo from the tissues like the retina. Here we aimed to assess the metabolic changes in the retina of patients with multiple sclerosis (MS). Methods We built a Raman spectroscopy prototype by connecting a scanning laser ophthalmoscope to a spectrophotometer. We defined the spectra of 10 molecules participating on energy supply, axon biology, or synaptic damage, which have been shown to be altered in the brain of patients with MS: cytochrome C, flavin adenine dinucleotide (FAD), nicotinamide adenine dinucleotide (NADH), N-acetyl-aspartate (NAA), excitotoxicity, glutamate, amyloid β (Aβ), τ and α-synuclein (SNCA), phosphatidyl-ethanolamine, and phosphatidyl-choline. We studied these molecules in a prospective cohort of patients with MS, either in the chronic phase or during relapses of acute optic neuritis (AON). Results Significant changes to all these molecules were associated with age in healthy individuals. There was a significant decrease in NADH and a trend toward a decrease in NAA in patients with MS, as well as an increase in Aβ compared with healthy controls. Moreover, NADH and FAD increased over time in a longitudinal analysis of patients with MS, whereas Aβ diminished. In patients with acute retinal inflammation due to AON, there was a significant increase in FAD and a decrease in SNCA in the affected retina. Moreover, glutamate levels increased in the affected eyes after a 6-month follow-up. Conclusions Alterations of molecules related to axonal degeneration are observed during neuroinflammation and show dynamic changes over time, suggesting progressive neurodegeneration.

Cockayne syndrome is a rare autosomal recessive disease, also known as a progeria disorder, causing dwarfism, senile appearance and multiple systemic affections. Ophthalmic abnormalities are frequent, for example, in the forms of pigmentary retinopathy with low visual acuity. We present two genetic-confirmed cases with a detailed electrophysiological exploration of their retinal findings. Complete ophthalmic exploration is undertaken, including full-field electroretinogram under ISCEV guidelines and multifocal electroretinogram (RETI-scan science, Roland-Consult, Germany), ultra-wide-field retinography and autofluorescence (Optomap, Optos PLC, Dunfermline, Scotland, UK) and macular and retinal nerve fibre layer optical coherence tomography (Cirrus, Carl-Zeiss Meditec, Inc, Dublin, CA). Both cases presented with CSA/ERCC8 mutation and low visual acuity. Diffuse pigmentary retinopathy with macular atrophy was found in ultra-wide-field retinography and autofluorescence. Electrophysiological testing reported wide retinal dysfunction on both cone and rod system with macular involvement. Pigmentary retinopathy in CS could translate a wide dysfunction of the retina with major affection of external retinal layers of both cone and rod cells. Macular implication is also present and could explain progressive vision loss in such cases.

Visual impairment significantly alters the quality of life of people with Multiple Sclerosis (MS). The objective of this study was to identify predictors (independent variables) of visual outcomes, and to define their relationship with neurological disability and retinal atrophy when assessed by optical coherence tomography (OCT). We performed a cross-sectional analysis of 119 consecutive patients with MS, assessing vision using high contrast visual acuity (LogMar), 2.5% and 1.25% low contrast visual acuity (Sloan charts), and color vision (Hardy-Rand-Rittler plates). Quality of vision is a patient reported outcome based on an individual's unique perception of his or her vision and was assessed with the Visual Functioning Questionnaire-25 (VFQ-25) with the 10 neuro-ophthalmologic items. MS disability was assessed using the expanded disability status scale (EDSS), the MS functional composite (MSFC) and the brief repetitive battery-neuropsychology (BRB-N). Retinal atrophy was assessed using spectral domain OCT, measuring the thickness of the peripapillar retinal nerve fiber layer (pRNFL) and the volume of the ganglion cell plus inner plexiform layer (GCIPL). The vision of patients with MS was impaired, particularly in eyes with prior optic neuritis. Retinal atrophy (pRNFL and GCIPL) was closely associated with impaired low contrast vision and color vision, whereas the volume of the GCIPL showed a trend (p = 0.092) to be associated with quality of vision. Multiple regression analysis revealed that EDSS was an explanatory variable for high contrast vision after stepwise analysis, GCIPL volume for low contrast vision, and GCIPL volume and EDSS for color vision. The explanatory variables for quality of vision were high contrast vision and color vision. In summary, quality of vision in MS depends on the impairment of high contrast visual acuity and color vision due to the disease.

IMPORTANCE: Neuroprotective and remyelinating therapies are required for multiple sclerosis (MS), and acute optic neuritis (AON) is a potential condition to evaluate such treatments. OBJECTIVE: To comprehensively assess key biological and methodological aspects of AON trials for testing neuroprotection and remyelination in MS. DESIGN, SETTING, AND PARTICIPANTS: The AON-VisualPath prospective cohort study was conducted from February 2011 to November 2018 at the Hospital Clinic of University of Barcelona, Barcelona, Spain. Consecutive patients with AON were prospectively enrolled in the cohort and followed up for 18 months. Data analyses occurred from November 2018 to February 2019. EXPOSURES: Participants were followed up for 18 months using optical coherence tomography, visual acuity tests, and in a subset of 25 participants, multifocal visual evoked potentials. MAIN OUTCOMES AND MEASURES: Dynamic models of retinal changes and nerve conduction and their associations with visual end points; and eligibility criteria, stratification, and sample-size estimation for future trials. RESULTS: A total of 60 patients (50 women [83%]; median age, 34 years) with AON were included. The patients studied displayed early and intense inner retinal thinning, with a thinning rate of approximately 2.38 μm per week in the ganglion cell plus inner plexiform layer (GCIPL) during the first 4 weeks. Eyes with AON displayed a 6-month change in latency of about 20 milliseconds, while the expected change in the eyes of healthy participants by random variability was 0.13 (95% CI, −0.80 to 1.06) milliseconds. The strongest associations with visual end points were for the 6-month intereye difference in 2.5% low-contrast letter acuity, which was correlated with the peripapillary retinal nerve fiber layer thinning (adjusted R(2), 0.57), GCIPL thinning (adjusted R(2), 0.50), and changes in mfVEP latency (adjusted R(2), 0.26). A 5-letter increment in high-contrast visual acuity at presentation (but not sex or age) was associated with 6-month retinal thinning (1.41 [95% CI, 0.60-2.23] μm less peripapillary retinal nerve fiber layer thinning thinning; P = .001; adjusted R(2), 0.20; 0.86 [95% CI, 0.35-1.37] μm less GCIPL thinning; P = .001; adjusted R(2), 0.19) but not any change in multifocal visual evoked potential latency. To demonstrate 50% efficacy in GCIPL thinning or change in multifocal visual evoked potential latency, a 6-month, 2-arm, parallel-group trial would need 37 or 50 participants per group to test a neuroprotective or remyelinating drug, respectively (power, 80%; α, .05). CONCLUSIONS AND RELEVANCE: Acute optic neuritis is a suitable condition to test neuroprotective and remyelinating therapies after acute inflammation, providing sensitive markers to assess the effects on both processes and prospective visual recovery within a manageable timeframe and with a relatively small sample size.