Temporal visual resolution and disease severity in MS

ObjectiveTo examine temporal visual resolution assessed as critical flicker frequency (CFF) in patients with MS and to investigate associations with visual system damage and general disability and cognitive function.MethodsThirty-nine patients with MS and 31 healthy controls (HCs) were enrolled in this cross-sectional study and underwent CFF testing, high- and low-contrast visual acuity, alertness and information processing speed using the paced auditory serial addition task (PASAT), and retinal optical coherence tomography (OCT). In patients with MS, visual evoked potentials (VEPs) and Expanded Disability Status Scale (EDSS) scores were assessed.ResultsCFF in patients with MS (mean ± SD: 40.9 ± 4.4 Hz) was lower than in HCs (44.8 ± 4.4 Hz, p < 0.001). There was no significant CFF difference between eyes with and without previous optic neuritis (ON). CFF was not associated with visual acuity, VEP latency, the peripapillary retinal nerve fiber layer thickness, and the combined ganglion cell and inner plexiform layer volume. Instead, reduced CFF was associated with worse EDSS scores (r2 = 0.26, p < 0.001) and alertness (r2 = 0.42, p = 0.00042) but not with PASAT (p = 0.33).ConclusionCFF reduction in MS occurs independently of ON and structural visual system damage. Its association with the EDSS score and alertness suggests that CFF reflects global disease processes and higher cortical processing rather than focal optic nerve or retinal damage.

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Neuro-Retina Might Reflect Alzheimer’s Disease Stage

Journal of Alzheimer s Disease ◽

10.3233/jad-200043 ◽

2020 ◽

Vol 77 (4) ◽

pp. 1455-1468

Author(s):

Roberto Santangelo ◽

Su-Chun Huang ◽

Maria Paola Bernasconi ◽

Monica Falautano ◽

Giancarlo Comi ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Plexiform Layer ◽

Cross Sectional Study ◽

Disease Stage ◽

Inner Plexiform Layer ◽

Fiber Layer ◽

Cross Sectional ◽

Rnfl Thickness ◽

Present Cross Sectional Study

Background: Alzheimer’s disease (AD) pathological hallmarks were found in retinas of AD patients. Several studies showed a significant reduction of neuro-retina thickness measured through optical coherence tomography (OCT) in AD patients, but possible correlations between retina morphology, cognition, and cerebrospinal fluid (CSF) AD biomarkers (Aβ42, t-tau, and p-tau) have been poorly investigated so far. Objective: In the present cross-sectional study, we measured the thickness of neuro-retinal layers through OCT searching for possible correlations with patients’ cognitive performances and CSF AD biomarkers. Methods: 137 consecutive subjects [43 with AD, 37 with mild cognitive impairment (MCI), and 57 healthy controls (HC)], received an OCT scan acquisition to measure the peripapillary retinal nerve fiber layer (RNFL) thickness. In a subsample of 21 AD, 18 MCI, and 18 HC, the macular volume of ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer was computed. A comprehensive neuropsychological assessment and CSF AD biomarkers’ concentrations were available in AD and MCI patients. Results: Peripapillary RNFL, global, and in superior quadrant was significantly thinner in AD and MCI patients when compared to HC, while macular GCL volume was significantly reduced only in AD. RNFL thickness in nasal and inferior quadrants was correlated with single CSF AD biomarker concentrations, but no differences were found in retina morphology depending on the presence of a CSF profile typical for AD. Memory performances were positively associated with GCL and IPL volume. Conclusion: Our findings might propose OCT as a reliable and easy to handle tool able to detect neuro-retinal atrophy in AD in relation with cognitive performances.

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Bilateral retinal pathology following a first-ever clinical episode of autoimmune optic neuritis

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000671 ◽

2020 ◽

Vol 7 (2) ◽

pp. e671 ◽

Cited By ~ 1

Author(s):

Carla A. Wicki ◽

Praveena Manogaran ◽

Tanja Simic ◽

James V.M. Hanson ◽

Sven Schippling

Keyword(s):

Visual Acuity ◽

Optic Neuritis ◽

Structural Damage ◽

Inner Plexiform Layer ◽

Fiber Layer ◽

Low Contrast ◽

Time Points ◽

Acute Optic Neuritis ◽

Retinal Pathology ◽

Clinical Episode

ObjectiveThis longitudinal study aimed to assess changes in retinal structure and visual function following a first-ever episode of acute optic neuritis (ON).MethodsClinical and optical coherence tomography (OCT) data obtained over a period of 12 months were retrospectively analyzed in 41 patients with a first-ever clinical episode of acute ON. OCT scans, high-contrast visual acuity (HCVA), and low-contrast visual acuity (LCVA) were acquired at baseline and at 1, 3, 6, and 12 months thereafter. Macular ganglion cell and inner plexiform layer (GCIP), peripapillary retinal nerve fiber layer (pRNFL), and macular inner nuclear layer (INL) thicknesses were assessed by OCT. Linear mixed-effects models were used to analyze OCT variables of ipsilateral ON and contralateral non-ON (NON) eyes over time.ResultsThe mean change of GCIP thickness in ON eyes was significant at all follow-up time points, with nearly 75% of the total reduction having occurred by month 1. In ON eyes, thinner GCIP thickness at month 1 correlated with lower LCVA at month 3. Mean pRNFL thickness in ON eyes differed significantly from NON eyes at all postbaseline time points. INL thickness was significantly increased in ON eyes (month 1) but also in contralateral NON eyes (month 12).ConclusionsRetinal structural damage develops rapidly following acute ON and is associated with subsequent functional visual deficits. Our results also suggest bilateral retinal pathology following unilateral ON, possibly caused by subclinical involvement of the contralateral NON eyes. Moreover, our data may assist in clinical trial planning in studies targeting tissue damage in acute ON.

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Macula structural and vascular differences in glaucoma eyes with and without high axial myopia

10.1101/2021.09.02.21263045 ◽

2021 ◽

Author(s):

Jasmin Rezapour ◽

Christopher Bowd ◽

Jade Dohleman ◽

Akram Belghith ◽

James A. Proudfoot ◽

...

Keyword(s):

Ganglion Cell ◽

Axial Length ◽

Plexiform Layer ◽

Positive Association ◽

Mean Deviation ◽

Ganglion Cell Complex ◽

Inner Plexiform Layer ◽

Fiber Layer ◽

Cross Sectional ◽

Axial Myopia

AbstractAimsTo assess the thickness of various retinal layers, and the superficial vessel density (sVD) in the macula of glaucomatous eyes and their associations with axial length (AL) and visual field mean deviation (VFMD) to identify parameters useful for glaucoma management in myopic eyes.Methods248 glaucoma patients (401 eyes) participating in the Diagnostic Innovations in Glaucoma Study observational cohort representing 3 axial myopia groups (non-myopia: n=146 eyes; mild myopia: n=208 eyes; high myopia (AL>26 mm): n=47 eyes) who completed macular OCT and OCT-Angiography imaging were included. The cross-sectional associations of AL and VFMD with the thickness of the ganglion cell inner plexiform layer (GCIPL), macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), sVD and macular choroidal thickness (mCT) were evaluated.ResultsThinner Global GCIPL and GCC were significantly associated with worse VFMD (R2=35.1%; and R2=33.4%; respectively p<0.001), but not with AL (all p>0.350). Thicker mRNFL showed a weak association with increasing AL (R2=3.4%; p=0.001) and a positive association with VFMD (global R2=20.5%; p<0.001). Lower sVD was weakly associated with increasing AL (R2=2.3%; p=0.016) and more strongly associated with more severe glaucoma VFMD (R2=31.8%; p<0.001). Thinner mCT was associated with increasing AL (R2=17.3% p<0.001) and not associated with VFMD (P=0.262). mRNFL was thickest while mCT was thinnest in all sectors of high myopic eyes.ConclusionsGCIPL and GCC thinned with increasing severity of glaucoma but were not significantly associated with axial length. GCIPL and GCC thickness may be useful clinical parameters to identify glaucoma in myopic eyes.

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Color vision is strongly associated with retinal thinning in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458511431972 ◽

2012 ◽

Vol 18 (7) ◽

pp. 991-999 ◽

Cited By ~ 44

Author(s):

Pablo Villoslada ◽

Ami Cuneo ◽

Jeffrey Gelfand ◽

Stephen L Hauser ◽

Ari Green

Keyword(s):

Multiple Sclerosis ◽

Visual Acuity ◽

Color Vision ◽

Color Discrimination ◽

Visual Pathway ◽

Visual Disability ◽

Fiber Layer ◽

Cross Sectional ◽

Low Contrast ◽

Sd Oct

Objectives: Multiple Sclerosis (MS) frequently causes injury to the anterior visual pathway (AVP), impairing quality of life due to visual dysfunction. Development of biomarkers in MS is a high priority and both low-contrast visual acuity (LCVA) and time-domain optical coherence tomography (TD-OCT) have been proposed as candidates for this purpose. We sought to assess whether psychophysical assessments of color vision are similarly correlated with structural measures of AVP injury, and therefore augment measures of visual disability in MS. Methods: We studied the association between high-contrast visual acuity (HCVA), LCVA, color vision (Hardy–Rand–Rittler plates (HRR) and Lanthony D15 tests) and OCT, using both high-resolution spectral-domain OCT (SD-OCT; Spectralis, Heidelberg Engineering, Germany) and TD-OCT (Stratus, Carl Zeiss, US) in a cohort of 213 MS patients (52 with previous optic neuritis) and 47 matched controls in a cross-sectional study. Results: We found that MS patients have impairments in HCVA and LCVA ( p < 0.001) but that they suffer from even more profound abnormalities in color discrimination ( p < 0.0001). We found strong correlation between color vision and SD-OCT measures of retinal nerve fiber layer (RNFL) thickness (average RNFL, r = 0.594, p < 0.001) and papillomacular bundle thickness ( r = −0.565, p < 0.001). The correlation between OCT scores and functional visual impairments of all types was much stronger for SD-OCT than for TD-OCT. Conclusion: Our results indicate that color vision is highly correlated with these OCT scores when compared with traditional measures of visual acuity. Also we found that SD-OCT is superior to TD-OCT for detecting anterior visual pathway damage in MS. This makes both color-visual measures and SD-OCT strong candidate biomarkers of disease progression.

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Microstructural visual system changes in AQP4-antibody–seropositive NMOSD

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000334 ◽

2017 ◽

Vol 4 (3) ◽

pp. e334 ◽

Cited By ~ 64

Author(s):

Frederike C. Oertel ◽

Joseph Kuchling ◽

Hanna Zimmermann ◽

Claudia Chien ◽

Felix Schmidt ◽

...

Keyword(s):

Visual System ◽

Diffusion Tensor ◽

Transverse Myelitis ◽

Plexiform Layer ◽

Inner Plexiform Layer ◽

Fiber Layer ◽

Foveal Thickness ◽

Microstructural Changes ◽

History Of ◽

Afferent Visual System

Objective:To trace microstructural changes in patients with aquaporin-4 antibody (AQP4-ab)-seropositive neuromyelitis optica spectrum disorders (NMOSDs) by investigating the afferent visual system in patients without clinically overt visual symptoms or visual pathway lesions.Methods:Of 51 screened patients with NMOSD from a longitudinal observational cohort study, we compared 6 AQP4-ab–seropositive NMOSD patients with longitudinally extensive transverse myelitis (LETM) but no history of optic neuritis (ON) or other bout (NMOSD-LETM) to 19 AQP4-ab–seropositive NMOSD patients with previous ON (NMOSD-ON) and 26 healthy controls (HCs). Foveal thickness (FT), peripapillary retinal nerve fiber layer (pRNFL) thickness, and ganglion cell and inner plexiform layer (GCIPL) thickness were measured with optical coherence tomography (OCT). Microstructural changes in the optic radiation (OR) were investigated using diffusion tensor imaging (DTI). Visual function was determined by high-contrast visual acuity (VA). OCT results were confirmed in a second independent cohort.Results:FT was reduced in both patients with NMOSD-LETM (p = 3.52e−14) and NMOSD-ON (p = 1.24e−16) in comparison with HC. Probabilistic tractography showed fractional anisotropy reduction in the OR in patients with NMOSD-LETM (p = 0.046) and NMOSD-ON (p = 1.50e−5) compared with HC. Only patients with NMOSD-ON but not NMOSD-LETM showed neuroaxonal damage in the form of pRNFL and GCIPL thinning. VA was normal in patients with NMOSD-LETM and was not associated with OCT or DTI parameters.Conclusions:Patients with AQP4-ab–seropositive NMOSD without a history of ON have microstructural changes in the afferent visual system. The localization of retinal changes around the Müller-cell rich fovea supports a retinal astrocytopathy.

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Age-dependent favorable visual recovery despite significant retinal atrophy in pediatric MOGAD: how much retina do you really need to see well?

Journal of Neuroinflammation ◽

10.1186/s12974-021-02160-9 ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Joachim Havla ◽

Thivya Pakeerathan ◽

Carolin Schwake ◽

Jeffrey L. Bennett ◽

Ingo Kleiter ◽

...

Keyword(s):

Visual Acuity ◽

Structural Damage ◽

Structural Changes ◽

Inner Plexiform Layer ◽

Visual Recovery ◽

Fiber Layer ◽

Initial Manifestation ◽

Low Contrast ◽

Age Related ◽

Retinal Atrophy

Abstract Background To investigate age-related severity, patterns of retinal structural damage, and functional visual recovery in pediatric and adult cohorts of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) optic neuritis (ON). Methods All MOGAD patients from the 5 participating centers were included. Patients with initial manifestation <18 years were included in the pediatric (MOGADped) cohort and patients with ≥18 years in the adult (MOGADadult) cohort. For patients with MOGAD ON, examinations at least ≥6 months after ON onset were included in the analyses. Using spectral domain optical coherence tomography (SD-OCT), we acquired peripapillary retinal nerve fiber layer thickness (pRNFL) and volumes of combined ganglion cell and inner plexiform layer (GCIPL). High- and 2.5% low-contrast visual acuity (HCVA, LCVA) and visual-evoked potentials (VEP) were obtained. Results Twenty MOGADped (10.3±3.7 years, 30 MOGAD ON eyes) and 39 MOGADadult (34.9±11.6 years, 42 MOGAD ON eyes) patients were included. The average number of ON episodes per ON eye was similar in both groups (1.8±1.3 and 2.0±1.7). In both pediatric and adult MOGAD, ON led to pronounced neuroaxonal retinal atrophy (pRNFL: 63.1±18.7 and 64.3±22.9 μm; GCIPL: 0.42±0.09 and 0.44±0.13 mm3, respectively) and moderate delay of the VEP latencies (117.9±10.7 and 118.0±14.5 ms). In contrast, visual acuity was substantially better in children (HCVA: 51.4±9.3 vs. 35.0±20.6 raw letters, p=0.001; LCVA: 22.8±14.6 vs. 13.5±16.4, p=0.028). Complete visual recovery (HCVA-logMAR 0.0) occurred in 73.3% of MOGADped and 31% MOGADadults ON eyes, while 3.3% and 31% demonstrated moderate to severe (logMAR > 0.5) visual impairment. Independent of retinal atrophy, age at ON onset significantly correlated with visual outcome. Conclusion Pediatric MOGAD ON showed better visual recovery than adult MOGAD ON despite profound and almost identical neuroaxonal retinal atrophy. Age-related cortical neuroplasticity may account for the substantial discrepancy between structural changes and functional outcomes.

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Determinants of vessel defects in superficial and deep vascular layers in normal-tension glaucoma using optical coherence tomography angiography

Scientific Reports ◽

10.1038/s41598-021-89428-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jiyun Lee ◽

Chan Kee Park ◽

Hae-Young Lopilly Park

Keyword(s):

Optical Coherence Tomography ◽

Optical Coherence Tomography Angiography ◽

Deep Layer ◽

Plexiform Layer ◽

Normal Tension Glaucoma ◽

Mean Deviation ◽

Inner Plexiform Layer ◽

Optical Coherence ◽

Fiber Layer ◽

Cross Sectional

AbstractWe investigated the characteristics of localized vessel density defects (VD) either in the deep or superficial vascular layer of normal-tension glaucoma patients using optical coherence tomography angiography (OCTA). In this retrospective, cross-sectional study, 74 eyes with localized retinal nerve fiber layer (RNFL) defect were included. The relationships between the widths of the VD in the superficial and deep layer and ocular factors were evaluated. Eyes with greater deep VD were significantly older (P = 0.023). The IOP measured at OCTA exam was significantly related to the width of the deep VD (P = 0.009). By contrast, average ganglion cell inner plexiform layer thickness (GCIPLT) was substantially related to the width of the superficial VD (P = 0.004). In logistic regression analysis, aging was noticeably associated with wider deep VD, whereas worse mean deviation (MD) had a significant association with wider superficial VD (P = 0.001, P = 0.003, respectively). In sum, while changes of the superficial layer seemed an overall ramification of glaucomatous damages, the deep layer was more likely to be affected by factors related to ocular microcirculation, such as IOPs and older age. Thus, looking into the deep vascular layer using OCTA could identify risk factors related to the disturbance in ocular microcirculation.

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Aquaporin-4 IgG seropositivity is associated with worse visual outcomes after optic neuritis than MOG-IgG seropositivity and multiple sclerosis, independent of macular ganglion cell layer thinning

Multiple Sclerosis Journal ◽

10.1177/1352458519864928 ◽

2019 ◽

Vol 26 (11) ◽

pp. 1360-1371 ◽

Cited By ~ 13

Author(s):

Elias S Sotirchos ◽

Angeliki Filippatou ◽

Kathryn C Fitzgerald ◽

Sara Salama ◽

Santiago Pardo ◽

...

Keyword(s):

Multiple Sclerosis ◽

Optic Neuritis ◽

Ganglion Cell ◽

Plexiform Layer ◽

Cross Sectional Study ◽

Aquaporin 4 ◽

Inner Plexiform Layer ◽

Cross Sectional ◽

Visual Outcomes ◽

Spectral Domain Oct

Background: Comparative studies of characteristics of optic neuritis (ON) associated with myelin oligodendrocyte glycoprotein-IgG (MOG-ON) and aquaporin-4-IgG (AQP4-ON) seropositivity are limited. Objective: To compare visual and optical coherence tomography (OCT) measures following AQP4-ON, MOG-ON, and multiple sclerosis associated ON (MS-ON). Methods: In this cross-sectional study, 48 AQP4-ON, 16 MOG-ON, 40 MS-ON, and 31 healthy control participants underwent monocular letter-acuity assessment and spectral-domain OCT. Eyes with a history of ON >3 months prior to evaluation were analyzed. Results: AQP4-ON eyes exhibited worse high-contrast letter acuity (HCLA) compared to MOG-ON (−22.3 ± 3.9 letters; p < 0.001) and MS-ON eyes (−21.7 ± 4.0 letters; p < 0.001). Macular ganglion cell + inner plexiform layer (GCIPL) thickness was lower, as compared to MS-ON, in AQP4-ON (−9.1 ± 2.0 µm; p < 0.001) and MOG-ON (−7.6 ± 2.2 µm; p = 0.001) eyes. Lower GCIPL thickness was associated with worse HCLA in AQP4-ON (−16.5 ± 1.5 letters per 10 µm decrease; p < 0.001) and MS-ON eyes (−8.5 ± 2.3 letters per 10 µm decrease; p < 0.001), but not in MOG-ON eyes (−5.2 ± 3.8 letters per 10 µm decrease; p = 0.17), and these relationships differed between the AQP4-ON and other ON groups ( p < 0.01 for interaction). Conclusion: AQP4-IgG seropositivity is associated with worse visual outcomes after ON compared with MOG-ON and MS-ON, even with similar severity of macular GCIPL thinning.

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Pre- and Postnatal Damage to the Retro-Geniculate Visual Pathways Cause Retinal Degeneration Predictive for Visual Function

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.734193 ◽

2021 ◽

Vol 15 ◽

Author(s):

Finn Lennartsson ◽

HannaMaria Öhnell ◽

Lena Jacobson ◽

Maria Nilsson

Keyword(s):

Visual System ◽

Plexiform Layer ◽

Visual Pathways ◽

Research Report ◽

Inner Plexiform Layer ◽

Fiber Tractography ◽

Fiber Layer ◽

Teenagers And Young Adults ◽

Magnetic Resonance Imaging Mri ◽

And Function

To increase the understanding of the relationship between structure and function in individuals with damage to the brain from different stages of maturation of the visual system, we examined 16 teenagers and young adults. We used diffusion-weighted magnetic resonance imaging (MRI) and fiber tractography of the optic radiation (OR) and optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell layer + inner plexiform layer (GC+IPL) in the macula. Visual field (VF) function was assessed with the Humphrey Field Analyzer (HFA). Injuries to the immature OR were associated with thinning of the pRNFL and GC+IPL, and corresponding VF defects irrespectively of timing of the lesion. However, in cases with bilateral white-matter damage of immaturity (WMDI) we noticed a well preserved central VF despite a very thin GC+IPL. We speculate that this is due to plasticity in the immature visual system. Similar results were not noticed among cases with unilateral damage, acquired pre- or postnatally, in which the central VF was affected in most cases. OCT has proved to be a valuable targeted tool in children with damage to the retro-geniculate visual pathways, and that focal thinning of the GC+IPL predicts VF defects. This brief research report includes a review of four previously published papers. In addition, we present one new case and apply a recently developed classification system for CVI. The classification was applied on cases with bilateral WMDI to investigate its relation to retinal structure.

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Cognitive impairment in patients with multiple sclerosis is associated with atrophy of the inner retinal layers

Multiple Sclerosis Journal ◽

10.1177/1352458517694090 ◽

2017 ◽

Vol 24 (2) ◽

pp. 158-166 ◽

Cited By ~ 17

Author(s):

Danko Coric ◽

Lisanne J Balk ◽

Merike Verrijp ◽

Anand Eijlers ◽

Menno M Schoonheim ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Plexiform Layer ◽

Strong Relationship ◽

Cognitively Impaired ◽

Retinal Layer ◽

Inner Plexiform Layer ◽

Fiber Layer ◽

Cross Sectional ◽

Potential Biomarker

Background: Inner retinal layer (IRL) atrophy is a potential biomarker for neurodegeneration in multiple sclerosis (MS). Objective: To investigate the relationship between cognitive impairment and IRL atrophy in MS. Methods: Cross-sectional study design, including 217 patients and 59 healthy controls. Subjects were investigated clinically, underwent retinal optical coherence tomography (OCT) and comprehensive cognitive assessments. The association between these modalities was evaluated by regression analyses. Results: Of the patients, 44.2% were cognitively impaired. In the absence of multiple sclerosis–associated optic neuritis (MSON), cognitively impaired patients had a significantly lower mean peripapillary retinal nerve fiber layer (pRNFL, Δ: 8.13 µm, p < 0.001) and mean macular ganglion cell–inner plexiform layer (mGCIPL, Δ: 11.50 µm, p < 0.001) thickness compared to cognitively preserved patients. There was a significant association between the presence of cognitive impairment and pRNFL (odds ratio (OR): 1.11, 95% confidence interval (CI): 1.04–1.18, p = 0.001) and mGCIPL (OR = 1.11, 95% CI = 1.05–1.18, p < 0.001) atrophy. This association was masked by the severe IRL atrophy seen following MSON. Conclusion: The strong relationship between cognitive impairment across multiple cognitive domains and atrophy of the pRNFL and mGCIPL in patients who never suffered from MSON suggests that OCT is useful in assessing central nervous system neurodegeneration in MS.

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