Early disability in ambulatory patients with multiple sclerosis: optical coherence tomography versus visual evoked potentials, a comparative study

Background: The aim was to compare the retinal nerve fibre layer (RNFL) thickness and visual evoked potentials (VEP) among eyes with multiple sclerosis (MS)‐associated optic neuritis, unaffected eyes of the same patients and eyes of disease‐free controls. Changes in RNFL thickness, visual acuity (VA) and VEP over time are evaluated in MS‐associated optic neuritis.Methods: Forty‐six eyes of 23 patients (six male and 17 female), who suffer from MS and were diagnosed with unilateral or bilateral optic neuritis, participated in the study. Forty eyes of 20 age‐ and gender‐matched controls were tested. VA measurement, optical coherence tomography and VEP were performed in all patients at presentation and at one, three and six months thereafter.Results: There was a statistically significant difference in VA between MS eyes with optic neuritis and controls (p < 0.0001), as well as between MS eyes with and without optic neuritis (p < 0.005). VA improved over time. Average RNFL thickness was reduced in MS eyes with or without optic neuritis in comparison to control eyes. This reduction in RNFL thickness was more marked over time. The amplitude of P100 was significantly decreased in MS eyes with optic neuritis in comparison to controls (p < 0.0001) and there was a statistically significant delay in peak time of P100 in MS eyes with optic neuritis versus the eyes of normal subjects (p < 0.0001), which improved over time.Conclusion: The present study suggests that there is a progressive decrease in RNFL over time in eyes with optic neuritis associated with MS. The amplitude and latency of P100 in VEP examination returned to normal ranges over time.

Vasospasm represents an early event in systemic sclerosis (SSc). Ocular vasospasm may induce optic nerve head (ONH) damage and has been involved in the pathogenesis of glaucoma, especially normal-tension glaucoma (NTG). We aimed to investigate the presence of structural abnormalities associated with NTG using swept-source optical coherence tomography (SS-OCT) and to correlate the OCT parameters with clinical, capillaroscopy and digital blood flow measures in patients with SSc. In this cross-sectional study, 40 patients with SSc and 23 age-matched controls were included. The following parameters were measured using SS-OCT: mean and sectoral retinal nerve fibre layer (RNFL) thickness, macular ganglion cell layer complex (GCC) thickness and ONH morphology. Nailfold capillaroscopy (NFC) and digital blood flow measurements using laser Doppler imaging (LDI) were performed in all subjects. Patients with SSc showed a thinner temporal RNFL than the controls (69.23 ± 11.74 versus 83.35 ± 20.19µm, p = 0.001). The other parameters were similar between the two groups. In SSc patients, there was an inverse correlation between the disease duration and the average, superior and inferior RNFL thickness and the GCC thickness and between Raynaud's phenomenon duration and the average RNFL and GCC thickness (p < 0.05). NFC and LDI measurements did not show correlations with OCT parameters. A thinner temporal RNFL and the correlation between Raynaud's phenomenon and disease duration and structural abnormalities on OCT suggest the presence of early ganglion cell damage in patients with SSc. Although mild, these findings indicate the need to monitor ocular abnormalities in SSc.

BackgroundMultiple sclerosis (MS) is an autoimmune disease that attacks the central nervous system, with optic neuritis (ON) being a common early manifestation. Retinal nerve fiber layer (RNFL) thickness may be a biomarker of neuroaxonal damage in MS patients. We sought to evaluate changes in RNFL thickness over 4 years in Omani MS patients with or without ON in comparison to a healthy control group.MethodsThis retrospective case-control study involved 27 MS patients and 25 healthy controls. Optical coherence tomography was performed upon first diagnosis and at a four-year follow-up. Differences in mean RNFL thickness were calculated.ResultsA total of 51 eyes from the MS group and 50 eyes from the control group were evaluated. There was a significant reduction in mean RNFL thickness among MS patients with ON at follow-up (81.21 versus 72.14 μm; P = .003), whereas no significant RNFL thinning was observed among MS patients without ON. However, there was a significant reduction in RNFL thickness among MS patients compared to healthy controls (76.79 versus 93.72 μm; P = .009), regardless of ON presence/absence.ConclusionsAxonal damage was seen in the optic nerves of Omani MS patients. Moreover, there was a significant reduction in RNFL thickness among MS patients with ON as the disease progressed; however, while there was evidence of RNFL thinning in MS patients without ON, this difference lacked statistical significance. Evaluation of RNFL thickness may represent a useful biomarker for monitoring disease progression in MS and its association with ON.

Objective To measure RNFL thickness by Frequency-domain optical coherence tomography (OCT) in patients with different stages of primary glaucoma (CACG and POAG),to evaluate the correlation between RNFL thickness and visual field mean defect (MD),to detect RNFL thickness change of early stage primary glaucoma,and to discuss the clinical significance in the early diagnosis of primary glaucoma objectively. Methods Ninety-two subjects of 40 normal and 52 with different stages of primary glaucoma were enrolled in this study.RNFL thickness was measured by Zeiss Cirru HD-OCT,and visual field was tested by Zeiss Humphrey-750.The association between visual field MD and RNFL thickness was evaluated with Pearson correlation coefficients. Results In the normal group,mean RNFL thickness was 112.91±9.36μm; the early period glaucoma group 94.43±7.67μm; the middle period glaucoma group 80.82±10.36μm; the later period glaucoma group 67.86±8.01μm.Visual field MD in each group was-0.88±1.53dB,-4.26±1.83dB,-7.43±2.64dB and -17.06±5.85dB.The differences in mean RNFL thickness and visual field MD between normal and each stage glaucoma group were significant (P ＜0.05) by independent sample t-test.In each stages of glaucoma group,mean RNFL thickness and visual field MD (early period:r =-0.537,middle period:r =-0.615,later period:r=-0.804) correlated significantly (P ＜0.05).In the early period glaucoma group,superior RNFL thickness was 116.32±11.65μm,inferior RNFL thickness 105.58±9.73μm,nasal RNFL thickness 75.40±10.91μm,and temporal RNFL thickness 70.28±13.08μm.In group B,superior RNFL thickness was 140.15±8.79μm,inferior RNFL thickness 137.29±10.07μm,nasal RNFL thickness 90.20±14.19μm,and temporal RNFL thickness 88.43±10.85μm.The difference of superior and inferior RNFL thickness between group A1 and group B had statistical significance tested by independent sample t-test,P ＜0.05; nasal and temporal RNFL thickness between group A1 and group B was tested by independent sample t-test,P ＞0.05,there was no statistical significance difference. Conclusions Frequency-domain OCT detected that the average of RNFL thickness become thinning with the progression of disease in the primary glaucoma patients,have negative correlation with vision MD,it is able to objectively reflect the degree of glaucomatous optic nerve damage.Frequency-domain OCT can show significantly decreased superior and inferior RNFL thickness of the early period primary glaucoma,which shows good ability in distinguishing normal from early period primary glaucomatous eyes. Key words: Optical coherence tomography (OCT); Retinal nerve fiber layer (RNFL); Mean defect (MD); Early diagnosis primary glaucoma

To study the significance of optic disc tomography and retinal nerve fiber layer (RNFL) thickness measurement by spectral-domain optical coherence tomography (OCT) in the diagnosis of glaucoma. It was a noninterventional, observational study. The optic disc topographic parameters and total and regional RNFL thickness were measured by RTVue OCT in 60 normal eyes and 97 glaucomatous eyes. One-way analysis of variance was used to compare the parameters above mentioned between normal and glaucomatous groups. The area under the receiver operating characteristic curve (AUC) and the sensitivity at 80% specificity were used to assess the ability of each testing parameter in the differentiation between normal and glaucoma eyes. There were statistically significant differences in all RTVue OCT measurement parameters (F = 1.024, P = 0.596;F = 36.519, 54.464, 27.659, 36.176, 20.562, 63.833, 30.031, 54.652, 98.146, 78.705, 99.839, 43.728, 75.720, 45.709, 39.380, 33.590, 66.887, 78.335, 45.485;P = 0.000) except disc area. The average RNFL thickness in normal, early, moderate and advanced glaucomatous eyes was 109.950, 93.313, 80.374 and 65.570 µm, respectively. Among the eight regions around the optic disc, the thickest RNFL was located at the inferotemporal (150.066 µm) and superotemporal (146.285 µm) regions in normal eyes, and the superotemporal (108.569, 103.420 and 88.708 µm in early, moderate and advanced glaucomatous eyes, respectively) and inferotemporal (108.201, 102.830 and 86.369 µm in early, moderate and advanced glaucomatous eyes, respectively) regions in glaucomatous eyes. Both in normal and glaucomatous eyes, the thinnest RNFL was located at the nasal and temporal regions, respectively. For optic disc topographic parameters, the highest AUC was vertical cup/disc ratio (AUC = 0.762, 0.946 and 0.988 in early, moderate and advanced glaucomatous eyes, respectively), and the sensitivity at 80% specificity was 62.2%, 76.5% and 99.2% in early, moderate and advanced glaucomatous eyes, respectively. For RNFL thickness, the highest AUC was superotemporal region RNFL thickness (AUC = 0.915) and the sensitivity at 80% specificity was 89.5% in early glaucomatous eyes. The highest AUC was inferior average RNFL thickness (AUC = 0.967) and the sensitivity at 80% specificity was 94.1% in moderate glaucomatous eyes. The highest AUC was average RNFL thickness (AUC = 0.985) and the sensitivity at 80% specificity was 99.2% in advanced glaucomatous eyes. Among the eight regions around the optic disc, RNFL thickness of region ST (AUC = 0.915, 0.926 and 0.966 in early, moderate and advanced glaucomatous eyes, respectively) achieved the highest AUC. RNFL thicknesses of the nasal and temporal regions showed the lowest AUCs. RTVue OCT shows fair discriminating ability in distinguishing normal from glaucomatous eyes. RTVue OCT is a useful equipment for the diagnosis of glaucoma.

PurposeCompare the retinal nerve fibre layer (RNFL) thickness in multiple sclerosis (MS) patients, with and without previous episodes of optic neuritis (ON), to disease‐free controls, using optical coherence tomography (OCT).MethodsThe RNFL was measured with a spectral domain OCT (Canon HS‐100) in 433 MS patients and in 70 controls. The MS eyes were sorted into three groups: MS non ON eyes (MSON−), MS ON eyes (MSON+) and the fellow eye of MS ON (MSON_fellow). One eye of each patient in the MSON‐group and in the control group was selected randomly for analysis.ResultsSeventy control eyes, 327 MSON‐ eyes, 106 MSON+ eyes and 106 MSON_fellow eyes were analysed in a linear regression adjusting for age. The average RNFL thickness was found to be statistically thinner in the MSON− group (88.2 ± 13.0 µm) compared to the controls (98.1 ± 9.0 µm; p &lt; 0.00).The average RNFL was thinner in the MSON+ group (77.3 ± 15.2 µm) compared to MSON− eyes and the controls (p &lt; 0.00). A paired t‐test showed a significant decrease in RNFL thickness in the MSON+ eyes compared to MSON_fellow.ConclusionsMultiple sclerosis causes RNFL loss. A mean reduction of ~10 µm was found in MS patients without history of ON and a mean reduction of 20 µm was found in MS patients with history of ON compared to healthy controls. This study showed that OCT is a useful tool that provides evidence of neural degeneration in MS patients, with or without the presence of ON.

Background Both functional and morphological changes in amblyopic development are known to occur at various levels in the central visual pathway.However,whether the retina is involved or not during amblyopic progression remains controversial.Objective This study was designed to compare the thicknesses of the fovea and retinal nerve fiber layer (RNFL) of the normal fellow eye of amblyopic eye using optical coherence tomography (OCT) in children with myopic anisometropia.Methods Twenty-two patients with unilateral myopic anisometropic amblyopia were included as the anisometropia amblyopia group.Ten unilateral myopic anisometropic amblyopia subjects received treatment and recovered were used as the amblyopic cure group,and 11 individuals with simple myopic anisometropia without amblyopia were enrolled as the control group.OCT was performed on both eyes of all the subjects with informed consent.Fovea retinal thickness and RNFL thickness from the superior,inferior,nasal and temporal quadrants in the peripapillary region were evaluated.The measurement parameters were bilaterally compared in all the individuals by paired t test.The multiple regression model was used to analyze the correlation of retinal thickness with amblyopia patients.This study was approved by the Ethic Committee of this hospital.Written informed consent was obtain from each subject prior to the eye examination.Results Fovea retinal thickness increased in the amblyopic eyes compared with the fellow eyes,showing a statistically significant difference between them (P =0.001).However,no significant differences were found in the fovea retinal thickness between both eyes in the amblyopic cure group and simple myopic anisometropia without amblyopia group (P =0.778,0.943).Among the anisometropia amblyopia group,amblyopia cure group and simple myopic anisometropia without amblyopia group,the RNFL thicknesses of the temporal quadrant was significantly thicker in the higher myopic lateral eyes than those of the fellow eyes (P＜0.001,P =0.003,P =0.046).However,the differences in the superior,inferior,nasal and the average RNFL thickness were not statistically significant between the two eyes (P＞0.05).A negative correlation was found between the inferior retinal thickness with age (r=-0.559,P=0.016).Conclusions The fovea may be affected in unilateral myopic anisometropic amblyopia.There is no significant difference in the RNFL thickness between simple myopic eye and unilateral myopic anisometropia amblyopic eye.Improvement in amblyopia is coming along with the reduction of the thickness of the fovea. Key words: Refractive error/myopia; Anisometropia; Amblyopia; Optical coherence tomography; Foveal thickness; Retinal nerve fiber layer thickness

To investigate the difference of retinal nerve fiber layer (RNFL) thickness and macular fovea thickness/volume between multiple sclerosis (MS) patients and healthy normal individuals using optical coherence tomography (OCT) and assess its association with visual field parameters. Thirty consecutive MS patients and 28 healthy controls were recruited in this prospective study. Comprehensive standardized ophthalmic examinations included visual acuity, cycloplegic refraction, intraocular pressure, gonioscopy, visual field, and RNFL thickness and macular fovea thickness/volume detection using Humphrey OCT. Mean values for the thickness of the peripapillary RNFL and macular volume were calculated. Associations between visual field parameters and RNFL thickness/macular volume were analyzed by Pearson correlation analysis. The RNFL thicknesses in each quadrant, the average macular thickness, and the average macular volume in MS patients were all less than those in healthy controls, with statistically significant differences. The RNFL thickness and macular fovea thickness/volume were greater in eyes without optic neuritis than in eyes with optic neuritis. The average visual field parameters had positive correlations with the RNFL thickness and negative correlations with macular parameters in MS patients. OCT measurements can effectively identify the nerve changes of MS patients, which provide more data for the diagnosis of MS.

Background and ObjectivesTo investigate the long-term effect of permanent demyelination on axonal attrition by examining an association between intereye asymmetry of the multifocal visual evoked potential (mfVEP) latency delay and subsequent thinning of retinal ganglion cell axons in patients with a long-standing history of unilateral optic neuritis (ON).MethodsOnly patients with a significant degree of chronic demyelination (intereye latency asymmetry >5 ms) were included in this study. The level of optic nerve demyelination was estimated at baseline by the latency delay of mfVEP, while the degree of axonal loss was assessed by thinning of the retinal nerve fiber layer (RNFL) thickness between baseline and follow-up visits. Low-contrast visual acuity (LCVA) was also evaluated at baseline and follow-up. Patients were examined twice with an average interval of 6.1 ± 1.4 years.ResultsFrom 85 examined patients with multiple sclerosis, 28 satisfied inclusion criteria. Latency of the mfVEP was delayed, and RNFL thickness was reduced in ON eyes compared with fellow eyes at both visits. There was significant correlation between latency asymmetry and baseline or follow-up intereye RNFL thickness asymmetry. Intereye asymmetry of LCVA at baseline correlated with baseline latency asymmetry of mfVEP and baseline asymmetry of RNFL thickness. Latency of the mfVEP in ON eyes improved slightly during the follow-up period, whereas latency of the fellow eye remained stable. By contrast, RNFL thickness significantly declined in both ON and fellow eyes during the follow-up period. The rate of RNFL thinning in ON eyes, however, was more than 2 times faster compared with the fellow eyes (p < 0.001). Furthermore, baseline latency asymmetry significantly correlated with the rate of RNFL thinning in ON eyes during the follow-up (p < 0.001), explaining almost half of the variability of temporal RNFL progression. For each millisecond of latency delay (i.e., ∼0.5 mm of demyelination along the optic nerve), temporal RNFL thickness was annually reduced by 0.05%.DiscussionOur study provides clear in vivo evidence that chronic demyelination significantly accelerates axonal loss. However, because this process is slow and its effect is mild, long-term monitoring is required to establish and confidently measure the neurodegenerative consequences of demyelination.

Optical coherence tomography as a tool for monitoring pediatric pseudotumor cerebri

Multiple sclerosis (MS) is characterized by demyelination, axonal degeneration, and inflammation. Corneal confocal microscopy has been used to identify axonal degeneration in several peripheral neuropathies. To assess corneal subbasal nerve plexus morphologic features, corneal dendritic cell (DC) density, and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with MS. This single-center, cross-sectional comparative study was conducted at a tertiary referral university hospital between May 27, 2016, and January 30, 2017. Fifty-seven consecutive patients with relapsing-remitting MS and 30 healthy, age-matched control participants were enrolled in the study. Corneal subbasal nerve plexus measures and DC density were quantified in images acquired with the laser scanning in vivo corneal confocal microscope, and peripapillary RNFL thickness was measured with spectral-domain optical coherence tomography. Corneal nerve fiber density, nerve branch density, nerve fiber length, DC density, peripapillary RNFL thickness, and association with the severity of neurologic disability as assessed by the Kurtzke Expanded Disability Status Scale (score range, 0-10; higher scores indicate greater disability) and Multiple Sclerosis Severity Score (score range, 0.01-9.99; higher scores indicate greater severity). Of the 57 participants with MS, 42 (74%) were female and the mean (SD) age was 35.4 (8.9) years; of the 30 healthy controls, 19 (63%) were female and the mean (SD) age was 34.8 (10.2) years. Corneal nerve fiber density (mean [SE] difference, -6.78 [2.14] fibers/mm2; 95% CI, -11.04 to -2.52; P = .002), nerve branch density (mean [SE] difference, -17.94 [5.45] branches/mm2; 95% CI, -28.77 to -7.10; P = .001), nerve fiber length (mean [SE] difference, -3.03 [0.89] mm/mm2; 95% CI, -4.81 to -1.25; P = .001), and the mean peripapillary RNFL thickness (mean [SE] difference, -17.06 [3.14] μm; 95% CI, -23.29 to -10.82; P < .001) were reduced in patients with MS compared with healthy controls. The DC density was increased (median [interquartile range], 27.7 [12.4-66.8] vs 17.3 [0-28.2] cells/mm2; P = .03), independent of a patient's history of optic neuritis. Nerve fiber density and RNFL thickness showed inverse associations with the Expanded Disability Status Scale (ρ = -0.295; P = .03 for nerve fiber density and ρ = -0.374; P = .004 for RNFL thickness) and the Multiple Sclerosis Severity Score (R = -0.354; P = .007 for nerve fiber density and R = -0.283; P = .03 for RNFL thickness), whereas other study measures did not. These data suggest that corneal confocal microscopy demonstrates axonal loss and increased DC density in patients with MS. Additional longitudinal studies are needed to confirm the use of corneal confocal microscopy as an imaging biomarker in patients with MS.

Assessment of structural and functıonal vısual outcomes ın relapsıng remıttıng multıple sclerosıs wıth vısual evoked potentıals and optıcal coherence tomography

Objective To investigate the relationship between retinal nerve fibre layer (RNFL) thickness and peripheral neuropathy in patients with type 2 diabetes. Methods Ninety-eight cases diagnosed with type 2 diabetes in the Department of Endocrinology in Beijing Hospital from March 2014 to June 2015 were enrolled in this study. Global and sectoral RNFL thicknesses were measured at 3.45 mm diameter around the optic nerve head using optical coherence tomography(OCT), and conduction velocity of peripheral nerve was measured in all cases. According to the diagnosis of diabetic neuropathies, participants were divided into 3 groups: non-diabetic peripheral neuropathy group(NDPN, n=36), subclinical diabetic peripheral neuropathy group(SDPN, n=37) and define diabetic peripheral neuropathy group(DDPN, n=25). RNFL thickness in different group was compared by analysis of variance and least-significant difference pairwise comparison. Results All sectoral RNFL thickness was thinning from NDPN group, SDPN group to DDPN group, specially inferior quadrant RNFL thickness, and there was significant difference among the three groups((132±19), (124±18) vs (116±17)μm, F=5.848, P=0.004). And significant difference was found in inferior quadrant RNFL thickness between NDPN and SDPN group(mean difference=8.67 μm, t=1.975, P=0.048), NDPN and DDPN group (mean differenc=16.59 μm, t=3.412, P=0.001). No significant difference was found in inferior quadrant RNFL thickness between SDPN and DDPN group(mean difference=7.93 μm, t=1.661, P=0.104). Covariance analysis showed that age and diabetes duration had no significant influence on RNFL thickness. Conclusions RNFL thickness maybe associated with diabetic peripheral neuropathy in patients with type 2 diabetes, especially in serious cases. Key words: Diabetes mellitus, type 2; Retinal nerve fibre layer; Diabetic peripheral neuropathy

Background: To investigate the retinal vessel diameter and its possible relationship with the retinal nerve fiber layer (RNFL) thickness in normal tension glaucoma (NTG). Methods: 86 NTG patients with detailed eye examination including retinal vessel analysis (DVA) and measurement of the RNFL thickness with scanning laser polarimetry (SLP; GDxVCC) were included in this retrospective study. The temporal retinal arteriolar diameters, temporal retinal venular diameters, vascular flicker response were compared with RNFL thickness and NFI (nerve fiber index). Results: The flicker response of DVA was significantly reduced as compared to normal eyes. The diameters of the temporal retinal arteriolar vessels were significantly correlated with RNFL thickness (P=0.0204) and NFI of GDxVCC (P=0.0021). The diameters of the temporal retinal venular were significantly correlated with the NFI (P=0.0298). Conclusion: Our results show that narrower arteriolar vessels are found in advanced NTG patients. These findings may be due to the decreased demand for retinal blood flow in damaged retina, but also may be one reason for the damage. Vessel analysis can contribute to the available tools predicting glaucomatous damage before visual field loss becomes manifest.

Purpose To establish and validate a formula to predict spectral‐domain optical coherence tomography (SD‐OCT) retinal nerve fiber layer (RNFL) thickness from time‐domain (TD)‐OCT RNFL measurements and other factors.Methods From healthy participants and patients with glaucoma, SD‐OCT and TD‐OCT scans were obtained on the same day. Univariate and multivariate linear regression relationships were analyzed to convert Stratus TD‐OCT measurements to Cirrus SD‐OCT measurements. Other baseline characteristics included were age, gender, intraocular pressure, central corneal thickness, spherical equivalent, anterior chamber depth, optic disc area, visual field mean deviation, and pattern standard deviation. The formula was generated using a training set of 220 patients and then evaluated on a validation dataset of 105 patients.Results Univariate analysis determined that TD‐OCT RNFL thickness, age, optic disc area, visual field mean deviation, and pattern standard deviation were significantly associated with SD‐OCT RNFL thickness. Multivariate stepwise regression analysis using available variables yielded the following equation: SD‐OCT RNFL = 0.746 × TD‐OCT RNFL + 17.104 (R2 = 0.879). In the validation sample, the multiple regression model explained 85.6% of the variance in the SD‐OCT RNFL thickness.Conclusion This formula based on TD‐OCT RNFL thickness may be useful in predicting SD‐OCT RNFL thickness. Other factors associated with SD‐OCT RNFL thickness, such as age, disc area, and mean deviation, did not contribute to the accuracy of the final equation.