Retinal Layer Atrophy Research Articles

Bile acid metabolites predict multiple sclerosis progression and supplementation is safe in progressive disease.

Bile acid metabolism is altered in multiple sclerosis (MS) and tauroursodeoxycholic acid (TUDCA) supplementation ameliorated disease in mouse models of MS. Global metabolomics was performed in an observational cohort of people with MS, followed by pathway analysis to examine relationships between baseline metabolite levels and subsequent brain and retinal atrophy. A double-blind, placebo-controlled trial was completed in people with progressive MS (PMS), randomized to receive either TUDCA (2 g/day) or placebo for 16weeks. Participants were followed with serial clinical and laboratory assessments. Primary outcomes were safety and tolerability of TUDCA, and exploratory outcomes included changes in clinical, laboratory, and gut microbiome parameters. In the observational cohort, higher primary bile acid levels at baseline predicted slower whole-brain atrophy, brain substructure atrophy, and specific retinal layer atrophy. In the clinical trial, 47 participants were included in our analyses (21 in placebo arm, 26 in TUDCA arm). Adverse events did not differ significantly between arms (p= 0.77). The TUDCA arm demonstrated increased serum levels of multiple bile acids. No significant differences were noted in clinical or fluid biomarker outcomes. Central memory CD4+ and Th1/17 cells decreased, while CD4+ naive cells increased in the TUDCA arm compared to placebo. Changes in the composition and function of gut microbiota were also noted between the two groups. Bile acid metabolism in MS is linked to brain and retinal atrophy. TUDCA supplementation in PMS is safe, tolerable, and has measurable biological effects that warrant further evaluation in larger trials with a longer treatment duration. National MS Society grant RG-1707-28601 to P.B., R01 NS082347 from the National Institute of Neurological Disorders and Stroke to P.A.C., and National MS Society grant RG-1606-08768 to S.S.

Choroid plexus volume as a marker of retinal atrophy in relapsing remitting multiple sclerosis

ObjectiveTo evaluate choroid plexus (CP) volume as a biomarker for predicting clinical disability and retinal layer atrophy in relapsing remitting multiple sclerosis (RRMS). MethodsNinety-five RRMS patients and 26 healthy controls (HCs) underwent 3 T whole brain MRI, expanded disability status scale (EDSS) and optical coherence tomography (OCT). Fully automated intra-retinal segmentation was performed to obtain the volumes of the retinal nerve fiber layer (RNFL), combined ganglion cell layer -inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), total macular volume (TMV) and papillomacular bundle (PMB). Automated segmentation of the CP within the lateral ventricles was performed and the choroid plexus volume (CPV) was normalized by total intracranial volume (TIV). Linear regression analysis and generalized estimating equation (GEE) models were applied to evaluate relationships between nCPV and EDSS, T2 lesion volume, disease duration, and retinal layer volumes, followed by Bonferroni correction analysis for multiple comparisons. ResultsRRMS patients had larger tChPV compared to HCs (p < 0.001). After Bonferroni correction, there was a significant positive correlation between tChPV and EDSS (r2 = 0.25, p = 0.0002), disease duration (r2 = 0.30, p = 0.01), and T2 lesion volume (r2 = 0.39, p = 0.0000). A robust negative correlation was found between tChPV and RNFL (p < 0.001), GCIPL (p = 0.003), TMV (p = 0.0185), PMB (p < 0.0001), G (p = 0.04), T(p = 0.0001). ConclusionsOur findings support the association of tChPV with disability and altered retinal integrity in RRMS.

Evaluation of Histopathologic Findings and Safety of Intravitreal Ketamine Administration on Vitreoretinal Tissue in Rat Model: A Pilot Study.

To evaluate the safety and histological findings of intravitreal injection of ketamine in rats. Each rat received a total volume of 0.1 ml of ketamine 0.01 mol/L (5 rats as ketamine group) or a total of 0.1 ml of normal saline 0.9% (5 rats as control group) under general anesthesia in a sterile condition. A histology assessment was performed 1 month after the intravitreal injection. Lens opacity, necrosis, and atrophy of retinal layers and optic disc were not seen in five specimens in the ketamine group and five in the normal saline group. There was no inflammation in the vitreous, retinal layers, choroid, optic disc, and optic nerve in both groups. Intravitreal injection of ketamine in a special dose has no obvious adverse effect on diverse intraocular tissue.

Characteristics and response of subretinal hyperreflective material to anti-vascular endothelial growth factor in myopic choroidal neovascularization

This retrospective study evaluated the characteristics and response of subretinal hyperreflective material (SHRM) to anti-vascular endothelial growth factor (VEGF) treatment in eyes with myopic choroidal neovascularization (CNV). The visual acuity (VA) was assessed at 3, 6, and 12 months after initiating anti-VEGF treatment in 116 patients (119 eyes) with SHRM and myopic CNV. Multimodal imaging, including color fundus photography, fluorescein angiography (FA), and optical coherence tomography angiography (OCT-A), were performed. We compared type 2 neovascularization (NV) (n = 64), subretinal hyperreflective exudation (SHE) (n = 37), NV with hemorrhage (n = 15), and fibrosis (n = 3). The type 2 NV group, and NV with hemorrhage groups showed significant VA improvement after 12 months of treatment (p < 0.05 in both groups); the SHE group failed to show improvement (p = 0.366). All groups showed a significant reduction in central foveal thickness after 12 months of treatment (all p < 0.05). The SHE group had a significantly higher incidence of interrupted ellipsoid zone than the other groups (p < 0.05). Myopic CNV can present as SHRM on OCT-A. Visual prognoses vary in different SHRM types. OCT-A and FA may help predict the outcomes of different subtypes of myopic CNV. SHE is predictive of outer retinal layer atrophy in patients with various SHRM types.

Mitochondrial measures in neuronally enriched extracellular vesicles predict brain and retinal atrophy in multiple sclerosis

Background: Mitochondrial dysfunction plays an important role in multiple sclerosis (MS) disease progression. Plasma extracellular vesicles are a potential source of novel biomarkers in MS, and some of these are derived from mitochondria and contain functional mitochondrial components. Objective: To evaluate the relationship between levels of mitochondrial complex IV and V activity in neuronally enriched extracellular vesicles (NEVs) and brain and retinal atrophy as assessed using serial magnetic resonance imaging (MRI) and optical coherence tomography (OCT). Methods: Our cohort consisted of 48 people with MS. NEVs were immunocaptured from plasma and mitochondrial complex IV and V activity levels were measured. Subjects underwent OCT every 6 months and brain MRI annually. The associations between baseline mitochondrial complex IV and V activities and brain substructure and retinal thickness changes were estimated utilizing linear mixed-effects models. Results: We found that higher mitochondrial complex IV activity and lower mitochondrial complex V activity levels were significantly associated with faster whole-brain volume atrophy. Similar results were found with other brain substructures and retinal layer atrophy. Conclusion: Our results suggest that mitochondrial measures in circulating NEVs could serve as potential biomarkers of disease progression and provide the rationale for larger follow-up longitudinal studies.

Natural history of retinal degeneration in ovine models of CLN5 and CLN6 neuronal ceroid lipofuscinoses

Neuronal ceroid lipofuscinoses (NCL; Batten disease) are a group of inherited neurodegenerative diseases with a common set of symptoms including cognitive and motor decline and vision loss. Naturally occurring sheep models of CLN5 and CLN6 disease display the key clinical features of NCL, including a progressive loss of vision. We assessed retinal histology, astrogliosis, and lysosomal storage accumulation in CLN5 affected (CLN5−/−) and CLN6 affected (CLN6−/−) sheep eyes and age-matched controls at 3, 6, 12, and 18 months of age to determine the onset and progression of retinal pathology in NCL sheep. The retina of CLN5−/− sheep shows progressive atrophy of the outer retinal layers, widespread gliosis, and accumulation of lysosomal storage in retinal ganglion cells late in disease. In contrast, CLN6−/− retina shows significant atrophy of all retinal layers, progressive gliosis, and earlier accumulation of lysosomal storage. This study has highlighted the differential vulnerability of retinal layers and the time course of retinal atrophy in two distinct models of NCL disease. This data will be valuable in determining potential targets for ocular therapies and the optimal timing of these therapies for protection from retinal dysfunction and degeneration in NCL.

Optical coherence tomography in multiple sclerosis: A 3-year prospective multicenter study.

ObjectiveTo evaluate changes over 3 years in the thickness of inner retinal layers including the peripapillary retinal nerve fiber layer (pRNFL), and combined macular ganglion cell and inner plexiform layers (mGCIPL), in individuals with relapsing‐remitting multiple sclerosis (RRMS) versus healthy controls; to determine whether optical coherence tomography (OCT) is sufficiently sensitive and reproducible to detect small degrees of neuroaxonal loss over time that correlate with changes in brain volume and disability progression as measured by the Expanded Disability Status Scale (EDSS).MethodsIndividuals with RRMS from 28 centers (n = 333) were matched with 64 healthy participants. OCT scans were performed on Heidelberg Spectralis machines (at baseline; 1 month; 6 months; 6‐monthly thereafter).ResultsOCT measurements were highly reproducible between baseline and 1 month (intraclass correlation coefficient >0.98). Significant inner retinal layer thinning was observed in individuals with multiple sclerosis (MS) compared with controls regardless of previous MS‐associated optic neuritis––group differences (95% CI) over 3 years: pRNFL: −1.86 (−2.54, −1.17) µm; mGCIPL: −2.03 (−2.78, −1.28) µm (both p < 0.0001; effect sizes 0.39 and 0.34). Greater inner retinal layer atrophy was observed in individuals diagnosed with RRMS <3 years versus >5 years (pRNFL: p < 0.05; mGCIPL: p < 0.01). Brain volume decreased by 1.3% in individuals with MS over 3 years compared to 0.5% in control subjects (effect size 0.76). mGCIPL atrophy correlated with brain atrophy (p < 0.0001). There was no correlation of OCT data with disability progression.InterpretationOCT has potential to estimate rates of neurodegeneration in the retina and brain. The effect size for OCT, smaller than for magnetic resonance imaging based on Heidelberg Spectralis data acquired in this study, was increased in early disease.

Association of retinal atrophy with cortical lesions and leptomeningeal enhancement in multiple sclerosis on 7T MRI

Background: Retinal atrophy in multiple sclerosis (MS) as measured by optical coherence tomography (OCT) correlates with demyelinating lesions and brain atrophy, but its relationship with cortical lesions (CLs) and meningeal inflammation is not well known. Objectives: To evaluate the relationship of retinal layer atrophy with leptomeningeal enhancement (LME) and CLs in MS as visualized on 7 Tesla (7T) magnetic resonance imaging (MRI). Methods: Forty participants with MS underwent 7T MRI of the brain and OCT. Partial correlation and mixed-effects regression evaluated relationships between MRI and OCT findings. Results: All participants had CLs and 32 (80%) participants had LME on post-contrast MRI. Ganglion cell/inner plexiform layer (GCIPL) thickness correlated with total CL volume (r =−0.45, p < 0.01). Participants with LME at baseline had thinner macular retinal nerve fiber layer (mRNFL; p = 0.01) and GCIPL (p < 0.01). Atrophy in various retinal layers was faster in those with certain patterns of LME. For example, mRNFL declined –1.113 (–1.974, –0.252) μm/year faster in those with spread/fill-pattern LME foci at baseline compared with those without (p = 0.01). Conclusion: This study associates MRI findings of LME and cortical pathology with thinning of retinal layers as measured by OCT, suggesting a common link between meningeal inflammation, CLs, and retinal atrophy in MS.

Socioeconomic Disparity Correlates with Faster Inner Retinal Layer Atrophy in Multiple Sclerosis (4179)

Socioeconomic Disparity Correlates with Faster Inner Retinal Layer Atrophy in Multiple Sclerosis (4179)

Three "Red Lines" for Pattern Recognition-Based Differential Diagnosis Using Optical Coherence Tomography in Clinical Practice.

Optical coherence tomography (OCT) devices for imaging of the eye are broadly available. The test is noninvasive, rapid, and well-tolerated by patients. This creates a large number of OCT images and patient referrals. Interpretation of OCT findings at the interface between neurological and ophthalmologic conditions has become a key skill in the neuro-ophthalmology service. Similar to the interpretation of visual fields, recogntion of the vertical and horizontal medians are helpful. A third "red line" is added, which will be reviewed here. Levels 1a to 5 evidence. Literature research. There is level 1a evidence that neurodegeneration of the brain is associated with inner retinal layer atrophy. Predominantly, this is driven by retrograde (trans-synaptic) axonal degeneration from the brain to the eye. This process typically stops at the level of the inner nuclear layer (INL). Anterograde (Wallerian) axonal degeneration from the eye to the brain can trespass the INL. The geography of atrophy and swelling of individual macular retinal layers distinguishes prechiasmal from postchiasmal pathology. The emerging patterns are a front-back "red line" at the INL; a vertical "red line" through the macula for chiasmal/postchiasmal pathology; and a horizontal "red line" through the macular for pathology pointing to the optic disc. This is summarized by illustrative case vignettes. The interpretation of patterns of individual retinal layer atrophy (3 "red lines") needs to be combined with recognition of localized layer thickening (edema, structural) at the macula. Certain macular patterns point to pathology at the level of the optic disc. This requires revision of the optic disc OCT and will guide need for further investigations. The 3 "red lines" proposed here may be found useful in clinical practice and the related mnemonics ("half moon," "sunset," "rainbow") for teaching.

Serum ceramide levels are altered in multiple sclerosis

Background: Sphingolipids are myelin components and inflammatory signaling intermediates. Sphingolipid metabolism may be altered in people with multiple sclerosis (PwMS), but existing studies are limited by small sample sizes. Objectives: To compare the levels of serum ceramides between PwMS and healthy controls (HCs) and to determine whether ceramide levels correlate with disability status, as well as optical coherence tomography (OCT)-derived rates of retinal layer atrophy. Methods: We performed targeted lipidomics analyses for 45 ceramides in PwMS (n = 251) and HCs (n = 68). For a subset of PwMS, baseline and 5-year Expanded Disability Status Scale (EDSS) assessments (n = 185), or baseline and serial spectral-domain OCT (n = 180) were assessed. Results: Several ceramides, including hexosylceramides, lactosylceramides, and dihydroceramides, were altered in PwMS compared with HCs. Higher levels of Cer16:0 were associated with higher odds of EDSS worsening at 5 years in univariable (odds ratio (OR) = 3.84, 95% confidence interval (CI) = 1.41–10.43) and multivariable analyses accounting for age, sex, and race (OR = 2.97, 95% CI = 1.03–8.59). Each 1 ng/mL higher concentration of Hex-Cer22:0 and DH-HexCer22:0 was associated with accelerated rates (μm/year) of ganglion cell + inner plexiform layer (–0.138 ± 0.053, p = 0.01; –0.158 ± 0.053, p = 0.003, respectively) and peripapillary retinal nerve fiber layer thinning (–0.305 ± 0.107, p = 0.004; –0.358 ± 0.106, p = 0.001, respectively). Conclusion: Ceramide levels are altered in PwMS and may be associated with retinal neurodegeneration and physical disability.

Progressive Multiple Sclerosis Is Associated with Faster and Specific Retinal Layer Atrophy.

Therapeutic development in progressive multiple sclerosis (PMS) has been hampered by a lack of reliable biomarkers to monitor neurodegeneration. Optical coherence tomography (OCT)-derived retinal measures have been proposed as promising biomarkers to fulfill this role. However, it is unclear whether retinal atrophy persists in PMS, exceeds normal aging, or can be distinguished from relapsing-remitting multiple sclerosis (RRMS). 178 RRMS, 186 PMS, and 66 control participants were followed with serial OCT for a median follow-up of 3.7 years. The estimated proportion of peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell + inner plexiform layer (GCIPL) thinning in multiple sclerosis (MS) attributable to normal aging increased from 42.7% and 16.7% respectively at age 25 years, to 83.7% and 81.1% at age 65 years. However, independent of age, PMS was associated with faster pRNFL (-0.34 ± 0.09%/yr, p < 0.001) and GCIPL (-0.27 ± 0.07%/yr, p < 0.001) thinning, as compared to RRMS. In both MS and controls, higher baseline age was associated with faster inner nuclear layer (INL) and outer nuclear layer (ONL) thinning. INL and ONL thinning were independently faster in PMS, as compared to controls (INL:-0.09 ± 0.04%/yr, p = 0.03; ONL:-0.12 ± 0.06%/yr, p = 0.04), and RRMS (INL:-0.10 ± 0.04%/yr, p = 0.01; ONL:-0.13 ± 0.05%/yr, p = 0.01), whereas they were similar in RRMS and controls. Unlike RRMS, disease-modifying therapies (DMTs) did not impact rates of retinal layer atrophy in PMS. PMS is associated with faster retinal atrophy independent of age. INL and ONL measures may be novel biomarkers of neurodegeneration in PMS that appear to be unaffected by conventional DMTs. The effects of aging on rates of retinal layer atrophy should be considered in clinical trials incorporating OCT outcomes. ANN NEUROL 2020;87:885-896.

Patterns of retrograde axonal degeneration in the visual system.

Conclusive evidence for existence of acquired retrograde axonal degeneration that is truly trans-synaptic (RTD) has not yet been provided for the human visual system. Convincing data rely on experimental data of lesions to the posterior visual pathways. This study aimed to overcome the limitations of previous human studies, namely pathology to the anterior visual pathways and neurodegenerative co-morbidity. In this prospective, longitudinal cohort retinal optical coherence tomography scans were acquired before and after elective partial temporal lobe resection in 25 patients for intractable epilepsy. Newly developed region of interest-specific, retinotopic areas substantially improved on conventional reported early treatment diabetic retinopathy study (ETDRS) grid-based optical coherence tomography data. Significant inner retinal layer atrophy separated patients with normal visual fields from those who developed a visual field defect. Acquired RTD affected the retinal nerve fibre layer, ganglion cell and inner plexiform layer and stopped at the level of the inner nuclear layer. There were significant correlations between the resected brain tissue volume and the ganglion cell layer region of interest (R = -0.78, P < 0.0001) and ganglion cell inner plexiform layer region of interest (R = -0.65, P = 0.0007). In one patient, damage to the anterior visual pathway resulted in occurrence of microcystic macular oedema as recognized from experimental data. In the remaining 24 patients with true RTD, atrophy rates in the first 3 months were strongly correlated with time from surgery for the ganglion cell layer region of interest (R = -0.74, P < 0.0001) and the ganglion cell inner plexiform layer region of interest (R = -0.51, P < 0.0001). The different time course of atrophy rates observed relate to brain tissue volume resection and suggest that three distinct patterns of retrograde axonal degeneration exist: (i) direct retrograde axonal degeneration; (ii) rapid and self-terminating RTD; and (iii) prolonged RTD representing a 'penumbra', which slowly succumbs to molecularly governed spatial cellular stoichiometric relationships. We speculate that the latter could be a promising target for neuroprotection.

Retinal atrophy in relation to visual functioning and vision-related quality of life in patients with multiple sclerosis

Background: Inner retinal layer atrophy in patients with multiple sclerosis (MS) has been validated as a structural imaging biomarker for neurodegeneration. Objective: To determine how retinal layer thickness relates to high-contrast visual acuity (HCVA), low-contrast visual acuity (LCVA) and vision-related quality of life (QoL) and to investigate the effect of previous episodes on MS-associated optic neuritis (MSON). Methods: Spectral-domain optical coherence tomography (SD-OCT) was performed in 267 patients with MS. Images were segmented for the peripapillary retinal nerve fiber layer (pRNFL) and the macular ganglion cell inner plexiform layer (GCIPL). Ophthalmological evaluations included history of MSON, HCVA, LCVA, and vision-related QoL. Results: Independent of MSON, HCVA and LCVA were significantly associated with pRNFL and GCIPL thicknesses. Vision-related QoL was positively associated with pRNFL (β = 0.92, p = 0.06) and GCIPL (β = 0.93, p = 0.02) thicknesses. These associations were independent of MSON. Not only binocular but also monocular atrophy of the inner retinal layers was associated with lower vision-related QoL. Conclusion: This study showed that retinal atrophy has a significant impact on visual functioning in patients with MS. OCT may therefore provide useful insight to patients with visual dysfunction, and our findings support including OCT and vision-related QoL measures into optic neuritis treatment trials.

Ganglion cell layer measurements correlate with disease severity in patients with Alzheimer's disease.

To evaluate the thickness of the 10 retinal layers of patients with Alzheimer's disease (AD) using a new segmentation technology of the Spectralis optical coherence tomography (OCT) and to determine whether the thickness of specific layers predicts neurodegeneration or AD severity. Patients with AD (n=150) and age-matched healthy controls (n=75) were analysed using the segmentation application prototype to automatically segment all retinal layers in a macular scan. Thicknesses of each layer were compared between patients with AD and controls, and between patients with disease durations of less than or at least 3years. Associations between retinal layer thicknesses, disease duration and AD severity were evaluated. Patients with AD had reduced thickness in the retinal nerve fibre, ganglion cell, inner plexiform and outer nuclear layers (p<0.05). The inner retinal layers were more affected in patients with long disease duration. Ganglion cell and retinal nerve fibre layer thicknesses were inversely correlated with AD duration and severity. Ganglion cell and inner plexiform layers thicknesses were predictive of axonal damage. The segmentation application revealed ganglion cell and retinal layer atrophy in patients with AD compared with controls, especially in the inner layers of patients with long disease duration. Ganglion cell layer reduction was associated with increased axonal damage and may predict greater disease severity.

Papillomacular bundle and inner retinal thicknesses correlate with visual acuity in nonarteritic anterior ischemic optic neuropathy.

To evaluate the ability of the papillomacular bundle (PMB) retinal nerve fiber layer and macular inner retinal layer thickness measurements with Spectralis optical coherence tomography (OCT) to differentiate eyes with nonarteritic anterior ischemic optic neuropathy (NAION) from uninvolved eyes and to evaluate whether their thicknesses correlate with visual acuity. An observational, cross-sectional study was performed, including 29 eyes with NAION and 29 uninvolved eyes from 29 patients. Eyes underwent scanning with Cirrus OCT (peripapillary and macular scanning) and Spectralis OCT (N-site axonal peripapillary scan and a new automated segmentation macular scan to measure individual retinal layers) in both eyes. The NAION eyes showed significant thinning versus uninvolved eyes in the macular retinal nerve fiber (P < 0.05), ganglion cell layer (GCL; P < 0.001), and inner plexiform layer (IPL; P < 0.01) by Spectralis and in the GCL-IPL by Cirrus (P < 0.02). Average and sectors of peripapillary retinal nerve fiber layer (pRNFL) and total macular thickness (TMT) were significantly reduced in NAION eyes, with both Spectralis and Cirrus OCT (P < 0.05). Spectralis temporal (ρSpearman = -0.768; P < 0.001) and PMB pRNFL thicknesses (ρSpearman = -0.675; P < 0.001), as well as central macular IPL thickness (ρSpearman = -0.735; P < 0.001), correlated strongly with best corrected visual acuity (BCVA). Quadratic regression using outer nasal TMT by Cirrus OCT and temporal pRNFL thickness by Spectralis were the best models to predict BCVA. Macular segmentation by Spectralis and Cirrus OCT revealed inner retinal layer atrophy in NAION eyes. The temporal and PMB pRNFL thicknesses and central macular IPL thickness by Spectralis-OCT and outer nasal TMT by Cirrus were strongly correlated with BCVA in NAION eyes.

Quality control for retinal OCT in multiple sclerosis: validation of the OSCAR-IB criteria

Background: Retinal optical coherence tomography (OCT) permits quantification of retinal layer atrophy relevant to assessment of neurodegeneration in multiple sclerosis (MS). Measurement artefacts may limit the use of OCT to MS research. Objective: An expert task force convened with the aim to provide guidance on the use of validated quality control (QC) criteria for the use of OCT in MS research and clinical trials. Methods: A prospective multi-centre (n = 13) study. Peripapillary ring scan QC rating of an OCT training set (n = 50) was followed by a test set (n = 50). Inter-rater agreement was calculated using kappa statistics. Results were discussed at a round table after the assessment had taken place. Results: The inter-rater QC agreement was substantial (kappa = 0.7). Disagreement was found highest for judging signal strength (kappa = 0.40). Future steps to resolve these issues were discussed. Conclusion: Substantial agreement for QC assessment was achieved with aid of the OSCAR-IB criteria. The task force has developed a website for free online training and QC certification. The criteria may prove useful for future research and trials in MS using OCT as a secondary outcome measure in a multi-centre setting.

Retinal hyperaemia-related blood vessel artifacts are relevant to automated OCT layer segmentation

A frequently observed local measurement artifact with spectral domain OCT is caused by the void signal of the retinal vasculature. This study investigated the effect of suppression of blood vessel artifacts with and without retinal hyperaemia. Spectral domain OCT scans, centred on the optic nerve head, were performed in 46 healthy subjects (92 eyes). Baseline scans were made during rest, while for the follow-up scan, 23 subjects (50 %) performed strenuous physical exercise. Systemic and retinal hyperaemia were quantified. Quantification of retinal nerve fibre layer (RNFL) thickness was performed with and without suppression of retinal blood vessel artifacts. The potential systematic effect on RNFL thickness measurements was analysed using Bland-Altman plots. At baseline (no retinal hyperaemia), there was a systematic difference in RNFL thickness (3.4 μm, limits of agreement -0.9 to 7.7) with higher values if blood vessel artifacts were not suppressed. There was significant retinal hyperaemia in the exercise group (p < 0.0001). Baseline thickness increased from 93.18 to 93.83 μm (p < 0.05) in the exercise group using the algorithm with blood vessel artifact suppression, but no significant changes were observed using the algorithm without blood vessel artifact suppression. Retinal hyperaemia leads to blood vessel artifacts which are relevant to the precision of OCT layer segmentation algorithms. The two algorithms investigated in this study can not be used interchangeably. The algorithm with blood vessel artifact suppression was more sensitive in detecting small changes in RNFL thickness. This may be relevant for the use of OCT in a range of neurodegenerative diseases were only a small degree of retinal layer atrophy have been found so far.

Retinal Layer Segmentation in Patients with Multiple Sclerosis Using Spectral Domain Optical Coherence Tomography

To evaluate the thickness of the 10 retinal layers in the paramacular area of patients with multiple sclerosis (MS) compared with healthy subjects using the new segmentation technology of spectral domain optical coherence tomography (OCT). To examine which layer has better sensitivity for detecting neurodegeneration in patients with MS. Observational, cross-sectional study. Patients with MS (n = 204) and age-matched healthy subjects (n = 138). The Spectralis OCT system (Heidelberg Engineering, Inc., Heidelberg, Germany) was used to obtain automated segmentation of all retinal layers in a parafoveal scan in 1 randomly selected eye of each participant, using the new segmentation application prototype. The thicknesses of 512 parafoveal points in the 10 retinal layers were obtained in each eye, and the mean thickness of each layer was calculated and compared between patients with MS and healthy subjects. The analysis was repeated, comparing patients with MS with and without previous optic neuritis. Correlation analysis was performed to evaluate the association between each retinal layer mean thickness, duration of disease, and functional disability in patients with MS. A logistic regression analysis was performed to determine which layer provided better sensitivity for detecting neurodegeneration in patients with MS. All retinal layers, except the inner limiting membrane, were thinner in patients with MS compared with healthy subjects (P < 0.05). Greater effects were observed in the inner retinal layers (nerve fiber, ganglion cells, inner plexiform, and inner nuclear layers) of eyes with previous optic neuritis (P < 0.05). The retinal nerve fiber layer and ganglion cell layer thicknesses were inversely correlated with the functional disability score in patients with MS. The ganglion cell layer and inner plexiform layer thicknesses could predict axonal damage in patients with MS. Analysis based on the segmentation technology of the Spectralis OCT revealed retinal layer atrophy in patients with MS, especially of the inner layers. Reduction of the ganglion cell and inner plexiform layers predicted greater axonal damage in patients with MS.

Distribution of Retinal Layer Atrophy in Patients With Parkinson Disease and Association With Disease Severity and Duration

To evaluate the thickness of the 10 retinal layers in the paramacular area of Parkinson disease patients using a new segmentation technology of optical coherence tomography (OCT) to examine whether the thickness of specific layers predicts neurodegeneration or Parkinson disease severity. Observational prospective study. Parkinson disease patients (n = 129) and age-matched healthy subjects (n = 129) were enrolled. The Spectralis OCT system was used to automatically segment all retinal layers in a parafoveal scan using the new segmentation application prototype. Mean thickness of each layer was calculated and compared between Parkinson disease patients and healthy subjects, and between Parkinson disease patients with disease durations of less than or at least 10 years. A correlation analysis was performed to evaluate the association between retinal layer thickness, duration of disease, and Parkinson disease severity. Logistic regression analysis was performed to determine the most sensitive layer for predicting axonal atrophy. Parkinson disease patients showed statistically significant reduced thickness in the retinal nerve fiber, ganglion cell, inner plexiform, and outer plexiform layers and increased thickness in the inner nuclear layer compared with healthy subjects (P < .05). The inner retinal layers were more affected in Parkinson disease patients with long disease duration. The ganglion cell layer thickness was inversely correlated with disease duration and Parkinson disease severity, and was predictive of axonal damage in Parkinson disease patients. The segmentation application of the Spectralis OCT revealed retinal layer atrophy in Parkinson disease patients, especially in the inner layers of patients with long disease duration. Ganglion cell layer reduction was associated with increased axonal damage.