Retinal Layer Thickness Measurements Research Articles

Ophthalmologic manifestations of adult patients with cystic fibrosis.

Cystic fibrosis (CF) is the most common life-shortening recessive genetic disease in Caucasians, affecting primarily the lungs. The objective of our study was to investigate potential ophthalmologic involvement in adult patients with CF. Fifty adult patients with cystic fibrosis and 60 age- and sex-matched controls underwent complete ophthalmologic examination including tear-film Break-Up Time (BUT), Macular Thickness, and peripapillary Retinal Nerve Fiber Layer (pRNFL) thickness measurements using Spectral Domain-OCT. CF patients had significantly lower nasal-inferior pRNFL thickness (median 82 IQR 67-102 vs 92.5 IQR 82-107, p = 0.005) and lower percentage of normal tear Break-Up Time (56.0% vs 96.7%, p = 0.001) than healthy controls. All CF patients with BUT <10 s were diagnosed with blepharitis at the time of our assessement. The subgroup of patients homozygous for the most common CF mutation, F508del, had lower nasal-inferior pRNFL thickness (p = 0.014) and lower percentage of normal tear Break-Up Time (p = 0.001) compared to the control group. Additional findings, present in the CF group only, were punctuate retinal hemorrhages (four patients), vessel tortuosity (four patients), snail-track degeneration, and retinal tufts (two patients without refractive error). There were no significant differences in visual acuity, refractive errors, gonioscopic findings, or intraocular pressure between the groups. Our study is, to the best of our knowledge, the largest ophthalmologic study of patients with cystic fibrosis. We found that CF patients had significantly decreased inferior-quadrant peripapillary retinal nerve fiber layer thickness and decreased tear-film break-up time compared to controls. We highlight the importance of careful regular ophthalmologic assessment and follow-up of these patients.

Temporal patterns of visual recovery following pituitary tumor resection: A prospective cohort study

Significant restoration of visual function can occur following pituitary tumor resection, although the time course of visual recovery remains poorly understood. This single-centre, two-year, prospective cohort study investigated the temporal patterns of visual recovery in consecutive patients undergoing pituitary tumor resection, between 2009 and 2018. Eyes were stratified based on pre-operative optical coherence tomography (OCT) retinal nerve fibre layer (RNFL) thickness measurements, with thin RNFL being defined as those within the fifth-percentile of age-matched normative values, and normal RNFL as those above the fifth-percentile. Visual function and OCT parameters were assessed pre-operatively, and at 6 weeks, 6 months, and 2 years post-operatively. 456 eyes of 228 patients (mean ± SD age, 53 ± 15 years) were included, of which 114 (25%) eyes had thin RNFL pre-operatively. Visual field recovery was observed in both groups during the first 6 weeks post-operatively (all Q ≤ 0.02), although improvements in visual field parameters between 6 weeks to 6 months were limited to eyes with thin RNFL (both Q < 0.05). No further improvements in visual function were detected beyond 6 months in both groups (both Q > 0.50). Similar trends were observed in linear regression analysis according to baseline visual function in both groups. In summary, eyes with normal RNFL thickness at baseline experienced most of their recovery within the first six weeks following surgery, while eyes with thin RNFL exhibited gradual improvements during the first six months. These findings have important implications when providing patient counselling and prognostication in the pre-operative setting.

A simplified combined index of structure and function for detecting and staging glaucomatous damage

Glaucomatous damage results in characteristics structural and functional changes on optical coherence tomography (OCT) imaging and standard automated perimetry (SAP) testing. The clinical utility of these measures differs based on disease severity, as they are evaluated along different measurement scales. This study therefore sought to examine if a simplified combined structure–function index (sCSFI) could improve the detection and staging of glaucomatous damage, compared to the use of average retinal nerve fiber layer thickness (RNFL) measurements from OCT and mean deviation (MD) values from SAP alone, and also an estimated retinal ganglion cell counts (eRGC) measure derived using empirical formulas described previously. Examining 577 eyes from 354 participants with perimetric glaucoma and 241 normal eyes from 138 healthy participants, we found that the sCSFI performed significantly better than average RNFL, MD and eRGC count for discriminating between glaucoma and healthy eyes (P ≤ 0.008 for all). The sCSFI also performed significantly better than RNFL and eRGC count at discriminating between different levels of visual field damage in glaucoma eyes (P < 0.001 for both). These findings highlight the clinical utility of combining structural and functional information for detecting and staging glaucomatous damage using the simplified index developed in this study.

The effects of ocular surface disease on optical coherence tomography test results in patients with glaucoma.

To evaluate the effects of current ocular surface disease (OSD) on OCT signal quality and peripapillary retinal nerve fiber layer (RNFL) thickness measurements in patients treated with antiglaucomatous medications and the changes in these test results by dry eye treatment. Fifty-five patients, diagnosed with primary open-angle glaucoma (POAG) and OSD, who were treated for glaucoma with topical medications for at least 6 months were included in this study. Patients were treated with topical preservative free polyvinyl alcohol + povidone artificial tear drops four times a day for at least 20 days and topical loteprednol etabonate drops four times a day for 1 week. Patients were divided into groups according to the number of active substances in their glaucoma drops, daily drop numbers, and duration of drug utilizations. OCT signal quality and mean RNFL thickness measurements were evaluated within these groups before and after OSD treatment. Pre-treatment mean OCT signal quality was 19.15 ± 3.739 and mean RNFL thickness was 93.07 ± 13.931µ; post-treatment mean OCT signal quality was 23.93 ± 3.839 and mean RNFL thickness was 98.27 ± 14.863 µ (p < 0.05). Post-treatment measurements were significantly improved compared to pre-treatment measurements in our patients, but the differences among subgroups were not statistically significant. There was a strong positive correlation between pre-treatment signal quality measurements and Schirmer II test values (p < 0.0001). Treatment of OSD in glaucoma patients being treated with long-term anti-glaucoma medications, seem to improve the quality and reliability of OCT test results.

Relationship between Retinal Nerve Fiber Layer Thickness and Cognitive Measures in Mild Cognitive Impairment Patients

Relationship between Retinal Nerve Fiber Layer Thickness and Cognitive Measures in Mild Cognitive Impairment Patients

Epiretinal Membrane Surgery: Structural Retinal Changes Correlate with the Improvement of Visual Function.

Several parameters have been studied for identifying the visual outcomes after pars plana vitrectomy (PPV) for epiretinal membrane (ERM) peeling. This retrospective study aimed to analyze structural retinal changes with spectral domain-optical coherence tomography (SD-OCT) and their correlations with visual acuity improvement in patients with ERM undergoing PPV. Twenty-one pseudophakic eyes were enrolled in the study. Ophthalmic evaluations included best corrected visual acuity (BCVA) and retinal layer thickness measurements with SD-OCT. The segmentation of the retina was divided into four parts: the inner retinal layer (IRL), composed of an internal limiting membrane, retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer; inner nuclear layer (INL); outer plexiform layer (OPL); and outer nuclear layer (ONL). Correlations between changes in retinal layer thicknesses and BCVA were explored over a 6 month follow-up period. The postoperative thickness decrease of the INL was significantly correlated with thickness changes in all other measured retinal layers (p < 0.001). Non-parametric linear regression showed that postoperative improvement in BCVA was associated with a postoperatively decreased thickness in the IRL (p = 0.021), INL (p = 0.039), and OPL (p = 0.021). In eyes undergoing PPV, postoperative thickness decreases of the IRL, INL, and OPL were correlated with visual acuity improvements. Re-compaction of these retinal layers after relieving ERM-induced traction may be an important factor in postoperative visual function improvement.

Retinal Sensitivity Thresholds Obtained Through Easyfield and Humphrey Perimeters in Eyes with Glaucoma: A Cross-Sectional Comparative Study.

ObjectiveTo compare global retinal sensitivity thresholds obtained through the Easyfield perimeter (EF) and Humphrey visual field analyzer (HFA).DesignObservational cross-sectional study.ParticipantsGlaucomatous patients and glaucoma suspects enrolled between October 2018 and April 2019.Materials and MethodsAll participants underwent EF (SPARK Precision) and HFA perimetry (SITA-Standard). After inclusion, demographic and ocular data were collected, including measurements of retinal nerve fiber layer (RNFL) thickness obtained from spectral-domain optical coherence tomography (SD-OCT). Global indices (mean deviation, MD; pattern standard deviation, PSD) values were compared between perimeters, and their correlation and agreement were evaluated. We used regression analysis to investigate structure-functional correlations between SD-OCT measurements and MD index of each perimeter.ResultsWe investigated 111 eyes from 69 patients. Mean MD (mean difference=1.49dB) and PSD values (mean difference=0.42dB) from the HFA were significantly larger than those from the EF perimeter (p<0.001). There were significant linear correlations between EF-MD and HFA-MD (r=0.56), and EF-PSD and HFA-PSD (r=0.38; p<0.001). We found significant non-linear associations between average RNFL thickness and MD values derived from both EF (R2=0.41) and HFA (R2=0.17) perimeters (p≤0.012). A difference <2dB between EF-MD and HFA-MD was found in 53% of the eyes, while 71% of them had a difference <1dB between EF-PSD and HFA-PSD.ConclusionWhile we found a moderate correlation and a small mean sensitivity difference between test results, EF’s correlation with structural measurements was at least comparable to that of the HFA. Our findings suggest that although these tests should not be used interchangeably, EF SPARK Precision could be used as an alternative for functional assessment in eyes with mild glaucoma.

Evaluation of the external validity of a joint structure\u2013function model for monitoring glaucoma progression

The dynamic structure–function (DSF) model was previously shown to have better prediction accuracy than ordinary least square linear regression (OLSLR) for short series of visits. The current study assessed the external validity of the DSF model by testing its performance in an independent dataset (Ocular Hypertension Treatment Study–Confocal Scanning Laser Ophthalmoscopy [OHTS–CSLO] ancillary study; N = 178 eyes), and also on different test parameters in a sample selected from the Diagnostic Innovations in Glaucoma Study or the African Descent and Glaucoma Evaluation Study (DIGS/ADAGES). Each model was used to predict structure–function paired data at visits 4–7. The resulting prediction errors for both models were compared using the Wilcoxon signed-rank test. In the independent dataset, the DSF model predicted rim area and mean sensitivity paired measurements more accurately than OLSLR by 1.8–5.5% (p ≤ 0.004) from visits 4–6. Using the DIGS/ADAGES dataset, the DSF model predicted retinal nerve fiber layer thickness and mean deviation paired measurements more accurately than OLSLR by 1.2–2.5% (p ≤ 0. 007). These results demonstrate the external validity of the DSF model and provide a strong basis to develop it into a useful clinical tool.

Study of Retinal Nerve Fiber Layer Thickness by Optical Coherence Tomography in Primary Open Angle Glaucoma, Glaucoma Suspect and Normal Nepalese Population

The measurement of retinal nerve fiber layer thickness can help significantly in the early diagnosis of glaucoma and monitoring of its progression. The objective of this study was to compare the retinal nerve fiber layer (RNFL) thickness by optical coherence tomography in primary open angle glaucoma, glaucoma suspects and normal Nepalese population. This was a hospital based cross-sectional study conducted in the Ophthalmology Out Patient Department of Manipal Teaching Hospital, Pokhara. Total 100 numbers of subjects (40 primary open angle glaucoma, 30 glaucoma suspects and 30 normal people) were evaluated. Complete ophthalmological examinations including tonometry, gonioscopy, optical coherence tomography, perimetry were performed. Statistical analysis was carried out using Epi-info 7. The result showed that the average retinal nerve fiber layer (RNFL) thickness was 70.22±12.07μm in right eye and 69.42±11.53μm in left eye in primary open angle glaucoma (POAG), 88.87±10.39μm in right eye and 88.73±9.59μm in left eye in glaucoma suspects (GS) and 94.40±9.21μm in right eye and 94.73±6.76μm in left eye in normal group respectively. The mean RNFL thickness was statistically significant in all three comparison groups except in nasal quadrant. The mean RNFL thickness was statistically significant in two comparison groups except in GS-Normal (nasal and temporal quadrant), GS-POAG (left nasal quadrant) and Normal-POAG (left nasal quadrant). The study concluded that the RNFL thickness is lower in POAG as compared to glaucoma suspects and normal group in the Nepalese population.

Examination of retinal vascular density changes via optical coherence tomography angiography in patients with glaucoma.

The aim of this study was to investigate the changes in vessel density (VD) in glaucoma patients and to investigate the relationship between VD and structural parameters using optical coherence tomography angiography. Our study included 25 primary open-angle glaucoma (POAG) patients, 25 pseudoexfoliation glaucoma (PXG) patients and 25 healthy individuals. All patients underwent 6 × 6mm retinal angiography (upper limit: internal limitan membrane [ILM], lower limit: 10µm inferior to inner plexiform layer) and 4.5 × 4.5mm disk angiography (upper limit: ILM, lower limit: posterior border of the retinal nerve fiber layer [RNFL]) via an optical coherence tomography (OCT) system (AngioVue, Optovue). Measures of vascular density were as follows: total area VD (tVD), intrapapillary VD (iVD), peripapillary VD (pVD) and parafoveal VD (pfVD). In addition to performing comparisons, the correlations between pVD, retinal nerve fiber layer (RNFL) thickness and optic nerve head measurement results were investigated. A total of 75 individuals were included in our study. In the POAG and PXG groups, tVD and pVD values were significantly lower than the control group (median tVDs were: 45.4, 45.9, 50.0, and median pVDs were: 50.0, 50.3, 53.1, respectively) (confidence intervals were: -9.8/-1.1 for pVD and -8.6/-1.4 for tVD). Significantly lower pf-VD values were detected in the PXG group compared to the control group (p < 0.05). There were strong positive correlations between RNFL thickness and pVD in in glaucoma groups (p < 0.001). There was no correlation between pVD and disk area, intraocular pressure and age in glaucoma patients. Patients using beta-blockers had significantly lower tVD and pVD values compared to those who did not (p < 0.05). The low VD values in glaucomatous eyes and the strong correlations between that values and RNFL thickness demonstrate a relationship between structural parameters and vascular parameters.

OCT Signal Enhancement with Deep Learning

To establish whether deep learning methods are able to improve the signal-to-noise ratio of time-domain (TD) OCT images to approach that of spectral-domain (SD) OCT images. Method agreement study and progression detection in a randomized, double-masked, placebo-controlled, multicenter trial for open-angle glaucoma (OAG), the United Kingdom Glaucoma Treatment Study (UKGTS). The training and validation cohort comprised 77 stable OAG participants with TD OCT and SD OCT imaging at up to 11 visits within 3 months. The testing cohort comprised 284 newly diagnosed OAG patients with TD OCT images from a cohort of 516 recruited at 10 United Kingdom centers between 2007 and2010. An ensemble of generative adversarial networks (GANs) was trained on TD OCT and SD OCT image pairs from the training dataset and applied to TD OCT images from the testing dataset. Time-domain OCT images were converted to synthesized SD OCT images and segmented via Bayesian fusion on the output of the GANs. Bland-Altman analysis assessed agreement between TD OCT and synthesized SD OCT average retinal nerve fiber layer thickness (RNFLT) measurements and the SD OCT RNFLT. Analysis of the distribution of the rates of RNFLT change in TD OCT and synthesized SD OCT in the two treatment arms of the UKGTS was compared. A Cox model for predictors of time-to-incident visual field (VF) progression was computed with the TD OCT and the synthesized SD OCT images. The 95% limits of agreement were between TD OCT and SD OCT were 26.64 to -22.95; between synthesized SD OCT and SD OCT were 8.11 to -6.73; and between SD OCT and SD OCT were 4.16 to -4.04. The mean difference in the rate of RNFLT change between UKGTS treatment and placebo arms with TD OCT was 0.24 (P= 0.11) and with synthesized SD OCT was 0.43 (P= 0.0017). The hazard ratio for RNFLT slope in Cox regression modeling for time to incident VF progression was 1.09 (95% confidence interval [CI], 1.02-1.21; P=0.035) for TD OCT and 1.24 (95% CI, 1.08-1.39; P= 0.011) for synthesized SD OCT. Image enhancement significantly improved the agreement of TD OCT RNFLT measurements with SD OCT RNFLT measurements. The difference, and its significance, in rates of RNFLT change in the UKGTS treatment arms was enhanced and RNFLT change became a stronger predictor of VF progression.

Cohort profile: a collaborative multicentre study of retinal optical coherence tomography in 539 patients with neuromyelitis optica spectrum disorders (CROCTINO)

PurposeOptical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease....

Editors' note: Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders

In the article “Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders,” Drs. Ringelstein et al. observed progressive delays in visual evoked potential (VEP) latency, occurring independently of acute optic neuritis, in 167 patients with neuromyelitis optica spectrum disorders (NMOSD) using 548 longitudinally assessed full-field VEP studies over the course of ≥3 months. In response, Dr. Chen seeks clarification about the authors' finding of a reduction in VEP amplitude with ≥3 months of follow-up but not among those with ≥12 months of follow-up. Dr. Chen wonders whether there may be similar correlations between VEP amplitude and disease activity as seen with optical coherence tomography (OCT) measurements of the peripapillary retinal nerve fiber layer thickness—which seem to decrease in NMOSD patients with non-ocular relapses vs those with stable disease—and calls for prospective longitudinal studies with VEP, OCT, and MRI to further explore this topic. Responding to these comments, the authors note that whereas their more restricted analysis of patients with ≥12 months of follow-up was intended to address the potential amplification of measurement variability that may have occurred with their interpolation of shorter-interval data—i.e., for patients with <12 months follow-up—their sample size may have been insufficient to achieve significance for analyses of amplitude changes. Nonetheless, they note that latency findings showed consistent and reliable increases in both the main and sub-analyses. This exchange highlights the ongoing evolution of our understanding about progressive tissue damage in NMOSD, previously thought to occur only in the context of relapses. We agree with Dr. Chen that longitudinal correlation of visual tests of structure, physiology, and function will be necessary to understand how frequently subclinical progressive disease might occur in NMOSD. In the article “Longitudinal optic neuritis-unrelated visual evoked potential changes in NMO spectrum disorders,” Drs. Ringelstein et al. observed progressive delays in visual evoked potential (VEP) latency, occurring independently of acute optic neuritis, in 167 patients with neuromyelitis optica spectrum disorders (NMOSD) using 548 longitudinally assessed full-field VEP studies over the course of ≥3 months. In response, Dr. Chen seeks clarification about the authors' finding of a reduction in VEP amplitude with ≥3 months of follow-up but not among those with ≥12 months of follow-up. Dr. Chen wonders whether there may be similar correlations between VEP amplitude and disease activity as seen with optical coherence tomography (OCT) measurements of the peripapillary retinal nerve fiber layer thickness—which seem to decrease in NMOSD patients with non-ocular relapses vs those with stable disease—and calls for prospective longitudinal studies with VEP, OCT, and MRI to further explore this topic. Responding to these comments, the authors note that whereas their more restricted analysis of patients with ≥12 months of follow-up was intended to address the potential amplification of measurement variability that may have occurred with their interpolation of shorter-interval data—i.e., for patients with <12 months follow-up—their sample size may have been insufficient to achieve significance for analyses of amplitude changes. Nonetheless, they note that latency findings showed consistent and reliable increases in both the main and sub-analyses. This exchange highlights the ongoing evolution of our understanding about progressive tissue damage in NMOSD, previously thought to occur only in the context of relapses. We agree with Dr. Chen that longitudinal correlation of visual tests of structure, physiology, and function will be necessary to understand how frequently subclinical progressive disease might occur in NMOSD.

Stereotactic radiosurgery for orbital cavernous venous malformation: a single center's experience for 15 years.

Stereotactic radiosurgery such as Gamma Knife radiosurgery (GKRS) has been shown to have a good treatment effect for orbital cavernous venous malformation (CVM). However, radiation-induced retinopathy or optic neuropathy is a vision-threatening complication of orbital irradiation. Predicting the post-treatment visual outcome is critical. Clinical and radiological outcomes were investigated in 30 patients who underwent GKRS for orbital CVM between July 2005 and February 2020. Measurement of peripapillary retinal nerve fiber layer (pRNFL) thickness using optical coherence tomography (OCT) was obtained in 14 patients. The median clinical and radiological follow-up periods were 46.6 months (range, 15.9-105.8) and 27.5 months (range, 15.4-105.8), respectively. Twenty-eight patients underwent multisession (4 fractions) GKRS. The median cumulative marginal dose was 20 Gy (range, 16-24). Two patients underwent single-session GKRS. Marginal doses were 15 Gy and 10.5 Gy in each patient. The volume of CVM decreased in 29 (97%) patients. Visual acuity was improved in 6 (20%) patients and was stable in 22 (73%) patients. Visual field defect and exophthalmos were improved in all patients. Serial investigation of OCT showed no statistically significant difference in pRNFL thickness after GKRS. Patients with normal average pRNFL thickness showed better visual recovery than patients with thin average pRNFL thickness. GKRS is an effective and safe treatment option for orbital CVM. The pRNFL thickness before GKRS can be a prognostic indicator for visual recovery in orbital CVM after GKRS.

Three-dimensional Neuroretinal Rim Thickness and Visual Fields in Glaucoma: A Broken-stick Model.

In open-angle glaucoma, when neuroretinal rim tissue measured by volumetric optical coherence tomography (OCT) scans is below a third of the normal value, visual field (VF) damage becomes detectable. To determine the amount of neuroretinal rim tissue thickness below which VF damage becomes detectable. In a retrospective cross-sectional study, 1 eye per subject (of 57 healthy and 100 open-angle glaucoma patients) at an academic institution had eye examinations, VF testing, spectral-domain OCT retinal nerve fiber layer (RNFL) thickness measurements, and optic nerve volumetric scans. Using custom algorithms, the minimum distance band (MDB) neuroretinal rim thickness was calculated from optic nerve scans. "Broken-stick" regression was performed for estimating both the MDB and RNFL thickness tipping-point thresholds, below which were associated with initial VF defects in the decibel scale. The slopes for the structure-function relationship above and below the thresholds were computed. Smoothing curves of the MDB and RNFL thickness covariates were evaluated to examine the consistency of the independently identified tipping-point pairs. Plots of VF total deviation against MDB thickness revealed plateaus of VF total deviation unrelated to MDB thickness. Below the thresholds, VF total deviation decreased with MDB thickness, with the associated slopes significantly greater than those above the thresholds (P<0.014). Below 31% of global MDB thickness, and 36.8% and 43.6% of superior and inferior MDB thickness, VF damage becomes detectable. The MDB and RNFL tipping points were in good accordance with the correlation of the MDB and RNFL thickness covariates. When neuroretinal rim tissue, characterized by MDB thickness in OCT, is below a third of the normal value, VF damage in the decibel scale becomes detectable.

Patterns of Retinal Ganglion Cell Damage in Nonarteritic Anterior Ischemic Optic Neuropathy Assessed by Swept-Source Optical Coherence Tomography.

To evaluate the ability of macular ganglion cell and inner plexiform layer (mGCIPL) and retinal nerve fiber layer (RNFL) thickness measurements by long-wavelength swept-source optical coherence tomography (SS-OCT) to assess retinal ganglion cell (RGC) damage in nonarteritic anterior ischemic optic neuropathy (NAION). A retrospective study of 20 patients with unilateral NAION was performed. SS-OCT scanning of the macular and peripapillary areas was performed to measure the total and six-sector thicknesses of macular RNFL (mRNFL) and mGCIPL, as well as peripapillary RNFL (pRNFL) thicknesses in global and 12 clock-hour sectors. Further comparison of these thicknesses between NAION involved eyes and uninvolved counterparts was performed in 12 of the 20 patients at 4 visits. The thickness map and en face images generated by volume data of the posterior pole over a 12 × 9-mm area were used for RNFL analysis. Median time intervals between the visual symptom onset and first thinning occurrences of mGCIPL, mRNFL, and pRNFL were 17 days (95% Confidence Interval [CI] 14-18 days), 43 days (95% CI 32-48 days), and 70 days (95% CI 62-80 days), respectively. The thickness map indicated a significantly reduced pRNFL in the superior temporal sectors or temporal sectors after 9 weeks, and retinal damage corresponded to the superior hemisphere's mRNFL and mGCIPL. En face images showed that the RNFL thinning area gradually expanded along the retinal nerve fiber direction and progressed toward the optic nerve head. The patterns of RGC damage in the macular and peripapillary areas of NAION eyes can be revealed by SS-OCT. Objective measurement of SS-OCT is valuable in characterizing NAION.

A 3D model to evaluate retinal nerve fiber layer thickness deviations caused by the displacement of optical coherence tomography circular scans in cynomolgus monkeys (Macaca fascicularis).

The main objective of the study was to analyze deviations in retinal nerve fiber layer (RNFL) thickness measurements caused by the displacement of circular optic disc optical coherence tomography scans. High-density radial scans of the optic nerve heads of cynomolgus monkeys were acquired. The retinal nerve fiber layer was manually segmented, and a surface plot of the discrete coordinates was generated. From this plot, the RNFL thicknesses were calculated and compared between accurately centered and intentionally displaced circle scans. Circle scan displacement caused circumpapillary retinal nerve fiber layer thickness deviations of increasing magnitude with increasing center offset. As opposed to the human eye, horizontal displacement resulted in larger RNFL thickness deviations than vertical displacement in cynomolgus monkeys. Acquisition of high-density radial scans allowed for the mathematical reconstruction and modelling of the nerve fiber layer and extrapolation of its thickness. Accurate and strictly repeatable circle scan placement is critical to obtain reproducible values, which is essential for longitudinal studies.

Efficiency of 123I-ioflupane SPECT as the marker of basal ganglia damage in acute methanol poisoning: 6-year prospective study

Context Investigate whether 123I-ioflupane SPECT (DaT SPECT) has the potential as a marker of basal ganglia damage in acute methanol poisoning. Methods Prospective, single-centre, cohort study of patients with confirmed methanol poisoning was conducted. DaT SPECT was performed twice with semi-quantification using DaTQUANTTM and MRI-based volumetry was calculated. Specific binding ratios (SBR) of striatum, caudate nucleus, and putamen were correlated with laboratory parameters of outcome, volumetric data, and retinal nerve fibres layer (RNFL) thickness measurements. Results Forty-two patients (mean age 46.3 ± 4.2 years; 8 females), including 15 with MRI-detected putamen lesions (group I) and 27 patients with intact putamen (group II), underwent DaT SPECT. Volumetry was calculated in 35 of the patients assessed. SBR values for the left putamen correlated with putamen volume (r = 0.665; p < 0.001). Decreased bilateral SBR values were determined for the striatum and the putamen, but not for the nucleus caudate, in group I (p < 0.05). Significant correlation was observed between the SBR of the posterior putamen and arterial blood pH (r = 0.574; p < 0.001) and other toxicological parameters of severity of poisoning/outcome including serum lactate, glucose, and creatinine concentrations (p < 0.05). The SBR of the posterior putamen positively correlated with the global RNFL thickness (p < 0.05). ROC analysis demonstrated a significant discriminatory ability of SBR of the posterior putamen with AUC = 0.753 (95%CI 0.604–0.902; p = 0.007). The multivariate regression model demonstrated that arterial blood pH, age, and gender were the most significant factors associated with SBR of the posterior putamen. Conclusion DaT SPECT demonstrates significant potential for the diagnosis of methanol-induced basal ganglia damage.

Conduction delays in the visual pathways of progressive multiple sclerosis patients covary with brain structure

In developed countries, multiple sclerosis (MS) is the leading cause of non-traumatic neurological disability in young adults. MS is a chronic demyelinating disease of the central nervous system, in which myelin is attacked, changing white matter structure and leaving lesions. The demyelination has a direct effect on white matter conductivity. This effect can be examined in the visual system, where damage is highly prevalent in MS, leading to substantial delays in conduction, commonly measured with visual evoked potentials (VEPs). The structural damage to the visual system in MS is often estimated with MRI measurements in the white matter. Recent developments in quantitative MRI (qMRI) provide improved sensitivity to myelin content and new structural methods allow better modeling of the axonal structure, leading researchers to link white matter microstructure to conduction properties of action potentials along fiber tracts. This study attempts to explain the variance in conduction latencies down the visual pathway using structural measurements of both the retina and the optic radiation (OR).Forty-eight progressive MS patients, participants in a longitudinal stem-cell therapy clinical trial, were included in this study, three and six months post final treatment. Twenty-seven patients had no history of optic neuritis, and were the main focus of this study. All participants underwent conventional MRI scans, as well as diffusion MRI and qMRI sequences to account for white matter microstructure. Optical coherence tomography scans were also obtained, and peripapillary retinal nerve fiber layer (pRNFL) thickness and macular volume measurements were extracted. Finally, latencies of recorded VEPs were estimated.Our results show that in non-optic neuritis progressive MS patients there is a relationship between the VEP latency and both retinal damage and OR lesion load. In addition, we find that qMRI values, sampled along the OR, are also correlated with VEP latency. Finally, we show that combining these parameters using PCA we can explain more than 40% of the inter-subject variance in VEP latency.In conclusion, this study contributes to understanding the relationship between the structural properties and conduction in the visual system in disease. We focus on the visual system, where the conduction latencies can be estimated, but the conclusions could be generalized to other brain systems where the white matter structure can be measured. It also highlights the importance of having multiple parameters when assessing the clinical stages of MS patients, which could have major implications for future studies of other white matter diseases.

Reproducibility of macular retinal nerve fiber layer and ganglion cell layer thickness measurements in a healthy pediatric population.

To evaluate the reproducibility of Spectralis spectral domain-OCT segmented ganglion cell layer (GCL) and macular retinal nerve fiber layer (mRNFL) measurements in a healthy children population. An observational, cross-sectional study was carried out on 79 children to measure the intraobserver reproducibility and the repeatability between a novel and an experienced operator of the segmented macular GCL and mRNFL. Interobserver and intraobserver reproducibility were defined by the intraclass correlation coefficient (ICC) and coefficients of variation (COV). Kruskal-Wallis test was used to determine statistical significance in the COV of three age groups children (younger than 6 years, between 6 and 12, and older than 12 years old). The results from the intraoperator GCL thickness analysis were highly reproducible (COV < 6%) and reliable (ICCs > 0.81). When the measurements were compared between a novel and an experienced examiner lower ICCs and higher COV were found. COVs ranged from 1.85% (total volume area) to 5.57% at the central ETDRS subfield while the ICC vary from 0.632 (outer inferior) to 0.832 (inner inferior). The repeatability and reproducibility of the mRNFL thickness were lower, with ICCs ranging from 0.428 to 0.872 in the interobserver analysis and from 0.897 to 0.346 in the interobserver one. In the present study, we establish substantial reliability of the GCL thickness in children with Spectralis® SD-OCT in all the sectors, albeit lower than the reported in the literature with other SD-OCTs and in adults. The reproducibility and repeatability of the mRNFL were significantly lower. We were unable to find consistent statistical significant differences between the COV of the three age groups.