In vivo evaluation of retinal neurodegeneration in patients with multiple sclerosis

Objective

To evaluate macular morphology in the eyes of patients with multiple sclerosis (MS) with or without optic neuritis (ON) in previous history.

Methods

Optical coherence tomography (OCT) examination was performed in thirty-nine patients with MS and in thirty-three healthy subjects. The raw macular OCT data were processed using OCTRIMA software. The circumpapillary retinal nerve fiber layer (RNFL) thickness and the weighted mean thickness of the total retina and 6 intraretinal layers were obtained for each eye. The eyes of MS patients were divided into a group of 39 ON-affected eyes, and into a group of 34 eyes with no history of ON for the statistical analyses. Receiver operating characteristic (ROC) curves were constructed to determine which parameter can discriminate best between the non-affected group and controls.

Results

The circumpapillary RNFL thickness was significantly decreased in the non-affected eyes compared to controls group only in the temporal quadrant (p = 0.001) while it was decreased in the affected eyes of the MS patients in all quadrants compared to the non-affected eyes (p<0.05 in each comparison). The thickness of the total retina, RNFL, ganglion cell layer and inner plexiform layer complex (GCL+IPL) and ganglion cell complex (GCC, comprising the RNFL and GCL+IPL) in the macula was significantly decreased in the non-affected eyes compared to controls (p<0.05 for each comparison) and in the ON-affected eyes compared to the non-affected eyes (p<0.001 for each comparison). The largest area under the ROC curve (0.892) was obtained for the weighted mean thickness of the GCC. The EDSS score showed the strongest correlation with the GCL+IPL and GCC thickness (p = 0.007, r = 0.43 for both variables).

Conclusions

Thinning of the inner retinal layers is present in eyes of MS patients regardless of previous ON. Macular OCT image segmentation might provide a better insight into the pathology of neuronal loss and could therefore play an important role in the diagnosis and follow-up of patients with MS.     

Correlation of Retinal Nerve Fibre Layer Thickness and Spontaneous Retinal Venous Pulsations in Glaucoma and Normal Controls

Purpose

To study the relationship between amplitude of spontaneous retinal venous pulsatility (SRVP) and retinal nerve fibre layer (RNFL) thickness in glaucomatous eyes, and to determine if this parameter may be a potential marker for glaucoma severity.

Method

85 subjects including 50 glaucoma (21 males, 67±10 yrs) and 35 normals (16 males, 62±11 yrs) were studied. SRVP amplitude was measured using the Dynamic Vessel Analyser (DVA, Imedos, Germany) at four regions of the retina simultaneously within one disc diameter from the optic disc—temporal-superior (TS), nasal-superior (NS), temporal-inferior (TI) and nasal-inferior (NI)). This was followed by RNFL thickness measurement using spectral domain optical coherence tomography (Spectralis OCT). The correlation between SRVP amplitude and corresponding sectoral RNFL thickness was assessed by means of non-linear regression (i.e. logarithmic). Linear regression was also applied and slopes were compared using analysis of covariance (ANCOVA).

Results

Greater SRVP amplitude was associated with thicker RNFL. Global SRVP amplitude was significantly lower in glaucoma eyes compared with normals (p<0.0001). The correlation coefficient of the linear regression between RNFL and SRVP at TS, NS, TI and NI quadrants in the glaucoma group were r = 0.5, 0.5, 0.48, 0.62. Mean SRVP amplitude and RNFL thickness for TS, NS, TI and NI quadrants were 4.3±1.5, 3.5±1.3, 4.7±1.6, 3.1±1 μm and 96±30, 75±22, 89±35 and 88±30 μm, respectively. The ANCOVA test showed that the slope of linear regression between the four quadrants was not significant (p>0.05). Since the slopes are not significantly different, it is possible to calculate one slope for all the data. The pooled slope equals 10.8 (i.e. RNFL = 10.8SRVP+41).

Conclusion

While SRVP was present and measurable in all individuals, the amplitude of SRVP is reduced in glaucoma with increasing RNFL loss. Our findings suggest the degree of SRVP may be an additional marker for glaucoma severity. Further studies are needed to determine the mechanism of reduction in SRVP, and whether changes can predict increased risk of progression.     

The impact of utilizing different optical coherence tomography devices for clinical purposes and in multiple sclerosis trials

Optical coherence tomography (OCT) derived retinal measures, particularly peri-papillary retinal nerve fiber layer (RNFL) thickness, have been proposed as outcome measures in remyelinating and neuroprotective trials in multiple sclerosis (MS). With increasing utilization of multiple centers to improve power, elucidation of the impact of different OCT technologies is crucial to the design and interpretation of such studies. In this study, we assessed relation and agreement between RNFL thickness and total macular volume (in MS and healthy controls) derived from three commonly used OCT devices: Stratus time-domain OCT, and Cirrus HD-OCT and Spectralis, two spectral-domain (SD) OCT devices. OCT was performed on both Cirrus HD-OCT and Stratus in 229 participants and on both Cirrus HD-OCT and Spectralis in a separate cohort of 102 participants. Pearson correlation and Bland-Altman analyses were used to assess correlation and agreement between devices. All OCT retinal measures correlated highly between devices. The mean RNFL thickness was 7.4 μm lower on Cirrus HD-OCT than Stratus, indicating overall poor agreement for this measurement between these machines. Further, the limits of agreement (LOA) between Cirrus HD-OCT and Stratus were wide (-4.1 to 18.9 μm), indicating poor agreement at an individual subject level. The mean RNFL thickness was 1.94 μm (LOA: -5.74 to 9.62 μm) higher on Spectralis compared to Cirrus HD-OCT, indicating excellent agreement for this measurement across this cohort. Although these data indicate that these three devices agree poorly at an individual subject level (evidenced by wide LOA in both study cohorts) precluding their co-utilization in everyday practice, the small difference for mean measurements between Cirrus HD-OCT and Spectralis indicate pooled results from these two SD-devices could be used as outcome measures in clinical trials, provided patients are scanned on the same machine throughout the trial, similar to the utilization of multiple different MRI platforms in MS clinical trials.     

Interocular Retinal Nerve Fiber Layer Thickness Difference in Normal Adults

PurposeTo determine the interocular retinal nerve fiber layer (RNFL) thickness difference of normal subjects.MethodsBoth eyes of 230 normal adults received peripapillary RNFL thickness measurements using OCT. The effect of ocular cyclotorsion on the RNFL thickness profile was mathematically corrected. The fractional and absolute interocular RNFL thickness differences at 256 points of peripapillary area were calculated. We divided the subjects into 3 groups according to the locations of superior and inferior peak thickness, respectively, and compared the interocular RNFL thickness differences between the subgroups.ResultsThe fractional interocular RNFL thickness difference exhibited smaller regional variations than the absolute interocular difference. The means of fractional interocular differences were 0.100 ± 0.077 in the temporal half area and 0.146 ± 0.105 in the nasal half area, and the tolerance limits for the 95th and 99th distributions were about 0.246 and 0.344 in the temporal half area and 0.293 and 0.408 in the nasal half area, respectively. The fractional interocular differences of subgroups classified by the locations of superior and inferior peak RNFL thickness showed difference at smaller areas than the absolute interocular differences (19 and 8 points versus 49 and 23 points, respectively).ConclusionGlaucoma can be strongly suspected, if interocular fractional RNFL thickness difference is over 25% at 5 consecutive points or over 35% at 3 consecutive points in the temporal half area. The fractional interocular comparison is a better diagnostic approach because the fractional interocular RNFL thickness difference is less influenced by the locations of peak RNFL thickness.     

Macular Thickness Measurements with Frequency Domain-OCT for Quantification of Retinal Neural Loss and its Correlation with Cognitive Impairment in Alzheimer?s Disease

PurposeTo evaluate the ability of frequency domain optical coherence tomography (fd-OCT) to estimate retinal neural loss in eyes with Alzheimer’s disease (AD). We also verified the existence of a correlation between AD-related cognitive impairment and macular and peripapillary retinal nerve fiber layer (RNFL) thickness measurements.Methodsfd-OCT scans were obtained from 45 eyes of 24 patients with AD and 48 control eyes. Peripapillary RNFL, macular full-thickness and segmented inner macular thickness parameters were calculated. The inner macular parameters included macular retinal nerve fiber layer (mRNFL) thickness, ganglion cell layer (GCL) plus inner plexiform layer thickness (GCL+), and RNFL plus GCL+ thickness (GCL++). The Mini-Mental State Examination (MMSE) was used to assess cognition in all subjects. The two groups were compared and the relationship between MMSE scores and fd-OCT measurements was verified.ResultsAverage, superior and inferior quadrant RNFL thickness parameters and all but one of the nine full-thickness macular measurements were significantly reduced in AD patients compared to controls. The segmented layers, GCL+ and GCL++ were significantly reduced in AD eyes. A significant correlation was found between most fd-OCT parameters (especially macular thickness measurements) and MMSE scores.ConclusionsMost fd-OCT peripapillary RNFL and macular full-thickness and segmented inner retinal layers parameters were reduced in AD eyes compared to controls. Moreover, neuronal loss, especially as reflected in macular parameters, correlated well with cognitive impairment in AD. Our results suggest that fd-OCT could be a potentially useful diagnostic tool in the evaluation and follow-up of AD patients.     

Differences of Intrasession Reproducibility of Circumpapillary Total Retinal Thickness and Circumpapillary Retinal Nerve Fiber Layer Thickness Measurements Made with the RS-3000 Optical Coherence Tomograph

Purpose

To evaluate the intrasession reproducibility of various thickness parameters used to diagnose and follow-up glaucoma, in particular circumpapillary total retinal thickness (cpTR) provided by the RS-3000 optical coherence tomograph (OCT).

Methods

Fifty-three healthy eyes of 28 subjects underwent three consecutive imaging with the RS-3000 Advance OCT (NIDEK, Aichi,Japan) to evaluate the intrasession reproducibility of circumpapillary total retinal thickness (cpTR), circumpapillary retinal nerve fiber layer thickness (cpRNFL), macular ganglion cell complex thickness (mGCC) and macular total retina thickness (mTR) measurements. Intraclass correlation (ICC), coefficient of variation (CV) and reproducibility coefficient (RC) were calculated for each parameter.

Results

The ICC and CV values for mean cpTR and cpRNFL were 0.987 and 0.897, and 0.60% and 2.81%, respectively. The RC values for the mean cpTR and cpRNFL were 5.95 μm and 9.04 μm, respectively. For all cpTR parameters the ICC values were higher and both the CV and RC values were lower than those for the corresponding cpRNFL parameters. The ICC and CV values for superior mGCC, inferior mGCC, superior mTR and inferior mTR were 0.983, 0.980, 0.983 and 0.988, and 0.84%, 0.98%, 0.48% and 0.43%, respectively. The RC values for superior mGCC, inferior mGCC, superior mTR and inferior mTR were 2.86 μm, 3.12 μm, 4.41μm and 4.43 μm, respectively.

Conclusions

Intrasession reproducibility of cpTR, mGCC and mTR measurements made on healthy eyes was high. Repeatability of cpTR measurements was better than that of the corresponding cpRNFL measurements. These results suggest that future clinical investigations addressing detection of glaucoma and glaucomatous progression with the RS-3000 OCT may benefit from focusing on the cpTR parameters.     

Comparison of Macular Integrity Assessment (MAIA ?), MP-3, and the Humphrey Field Analyzer in the Evaluation of the Relationship between the Structure and Function of the Macula

Purpose

This study was conducted in order to compare relationships between the macular visual field (VF) mean sensitivity measured by MAIA^TM (Macular Integrity Assessment), MP-3, or Humphry field analyzer (HFA) and the ganglion cell and inner plexiform layer (GCA) thicknesses.

Methods

This cross-sectional study examined 73 glaucoma patients and 19 normal subjects. All subjects underwent measurements for GCA thickness by Cirrus HD-OCT and static threshold perimetry using MAIA^TM, MP-3, or HFA. VF and OCT in the retinal view were used to examine both the global relationship between the VF sensitivity and GCA thickness, and the superior hemiretina and inferior hemiretina. The relationship between the GCA thickness and macular sensitivity was examined by Spearman correlation analysis.

Results

For each instrument, statistically significant macular VF sensitivity (dB) and GCA thickness relationships were observed using the decibel scale (R = 0.547–0.687, all P < 0.001). The highest correlation for the global (R = 0.682) and the superior hemiretina (R = 0.594) GCA thickness-VF mean sensitivity was observed by the HFA. The highest correlation for the inferior hemiretina (R = 0.687) GCA thickness-VF mean sensitivity was observed by the MP-3. Among the three VF measurement instruments, however, no significant differences were found for the structure-function relationships.

Conclusions

All three VF measurement instruments found similar structure-function relationships in the central VF.     

The influence of corneal astigmatism on retinal nerve fiber layer thickness and optic nerve head parameter measurements by spectral-domain optical coherence tomography

ABSTRACT: BACKGROUND: To evaluate the influence of corneal astigmatism (CA) on retinal nerve fiber layer (RNFL) thickness and optic nerve head(ONH) parameters measured with spectral-domain optical coherence tomography (OCT) in high myopes patients before refractive surgery. METHODS: Seventy eyes of 35 consecutive refractive surgery candidates were included in this study. The mean age of the subjects was 26.42 +/- 6.95 years, the average CA was 1.17 diopters (D; SD 0.64; range 0.2 to-3.3D), All subjects in this study were WTR CA. 34 eyes were in the normal CA group with a mean CA was 0.67 +/- 0.28D, 36 eyes were in the high CA group with an average CA of 1.65 +/- 0.49D. All subjects underwent ophthalmic examination and imaging with the Cirrus HD OCT. RESULTS: No significant difference was noted in the average cup-to-disk ratio, vertical cup-to-disk ratio and cup volume (all P values > 0.05). Compared with the normal CA group, the high CA group had a larger disc area and rim area, thinner RNFL thickness in the temporal quadrant, and the superotemporal and inferotemporal peaks were farther to the temporal horizon (All P values < 0.05). There were no significant differences between the two groups in global average RNFL thickness, as well as superior, nasal and inferior quadrant RNFL thickness (all P values > 0.05). CONCLUSIONS: The degree of with-the-rule CA should be considered when interpreting ONH parameters and peripapillary RNFL thickness measured by the Cirrus HD OCT. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1148475676881895.     

光学相干断层成像术在近视眼视网膜神经纤维层厚度测量中的临床应用

目的:研究光学相干断层成像术(OCT)在近视眼视网膜神经纤维层(RNFL)厚度测量中的应用价值。方法:选择2016年1月到2016年5月在医院就诊的近视患者73例(138眼)纳入此次研究,根据近视情况将患者分为低度近视组(-0.30D~-3.00D)共26例(48眼)、中度近视组(-3.01~-6.00D)共24例(47眼)及高度近视组(-6.00D)共23例(43眼)。另选同期在医院体检(视力正常)的健康志愿者25例(45眼)作为对照组,对比各组不同象限的RNFL厚度,屈光度及眼轴长度,分析近视眼各象限的RNFL厚度与患者屈光度和眼轴长度的相关性。结果:高度近视组的上方象限、下方象限以及鼻侧象限的RNFL厚度均明显低于对照组及中度近视组,中度近视组的下方象限及鼻侧象限的RNFL厚度均明显低于对照组,低度近视组鼻侧象限的RNFL厚度明显低于对照组,差异均有统计学意义(均P0.05)。近视组的屈光度及眼轴长度均明显大于对照组,且高度近视组均明显大于中度近视组与低度近视组,中度近视组均明显大于低度近视组,差异均有统计学意义(均P0.05)。根据Pearson法分析相关性可知,近视眼患者上象限、下象限、鼻侧象限的RNFL厚度与其屈光度及眼轴长度均呈负相关。结论:利用OCT技术检测近视眼RNFL厚度时,应考虑屈光度及眼轴长度可能造成的影响,综合进行分析判断,以获得最佳检测数值。     

Heterogeneous pattern of retinal nerve fiber layer in multiple sclerosis. High resolution optical coherence tomography: potential and limitations

Background

Recently the reduction of the retinal nerve fibre layer (RNFL) was suggested to be associated with diffuse axonal damage in the whole CNS of multiple sclerosis (MS) patients. However, several points are still under discussion. (1) Is high resolution optical coherence tomography (OCT) required to detect the partly very subtle RNFL changes seen in MS patients? (2) Can a reduction of RNFL be detected in all MS patients, even in early disease courses and in all MS subtypes? (3) Does an optic neuritis (ON) or focal lesions along the visual pathways, which are both very common in MS, limit the predication of diffuse axonal degeneration in the whole CNS? The purpose of our study was to determine the baseline characteristics of clinical definite relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients with high resolution OCT technique.

Methodology

Forty-two RRMS and 17 SPMS patients with and without history of uni- or bilateral ON, and 59 age- and sex-matched healthy controls were analysed prospectively with the high resolution spectral-domain OCT device (SD-OCT) using the Spectralis 3.5mm circle scan protocol with locked reference images and eye tracking mode. Furthermore we performed tests for visual and contrast acuity and sensitivity (ETDRS, Sloan and Pelli-Robson-charts), for color vision (Lanthony D-15), the Humphrey visual field and visual evoked potential testing (VEP).

Principal Findings

All 4 groups (RRMS and SPMS with or without ON) showed significantly reduced RNFL globally, or at least in one of the peripapillary sectors compared to age-/sex-matched healthy controls. In patients with previous ON additional RNFL reduction was found. However, in many RRMS patients the RNFL was found within normal range. We found no correlation between RNFL reduction and disease duration (range 9–540 months).

Conclusions

RNFL baseline characteristics of RRMS and SPMS are heterogeneous (range from normal to markedly reduced levels).     

The Impact of Structural and Functional Parameters in Glaucoma Patients on Patient-Reported Visual Functioning

Background

To evaluate the impact of structural changes of the retinal nerve fiber layer (RNFL), and visual field loss, on functional impairment assessed by patient-reported visual functioning in glaucoma.

Methods

Patients with glaucomatous optic nerve damage were enrolled in this cross-sectional study. Peripapillary RNFL thickness was obtained with spectral-domain optical coherence tomography (SD-OCT). Function was assessed by patient-reported visual functioning using the Rasch-calibrated Glaucoma Activity Limitation 9 (GAL-9) questionnaire and standard automated perimetry. The impact of peripapillary RNFL loss on functional impairment was analyzed with correlation and linear regression analyses.

Results

A total of 176 eyes from 88 glaucoma patients were included. The SD-OCT assessed temporal-superior and temporal-inferior RNFL sector of the worse eye revealed significant correlation with the GAL-9 scores (r=-0.298, p=0.011 and r=-0.251, p=0.033, respectively). In mutivariate regression analysis, the best predictors for patient-reported visual functioning were visual acuity of the better eye and mean defect of the worse eye (R²=0.334), while structural parameters could not enhance the prediction of GAL-9 scores.

Conclusions

Self-reported visual functioning of patients with glaucoma is better predicted by visual performance data than structural parameters. However, some structural changes of the worse eye are significantly correlated with patient-reported visual functioning.     

Preferential use of casing (girth) measures for estimating body volume and density.

Theoretical justification for the preferential use of casing (circumference) measurements for estimating total body volume (TBV) and body density (Db) was studied in 24 female subjects (mean age 20 yr, mean wt 58 kg). Multiple linear regression equations resulted in R = On-0.99 with a standard error no larger than 1.69 liters for predicting TBV and R = Oa-Oh with a standard error no larger than 0.0084 g/ml for predicting Db. Validations of these regression equations using two additional samples of subjects resulted in validity coefficients of r = 0 -0.99. All the correlation coefficients were statistically significant (P less than 0.01).     

The Effect of Axial Length on the Thickness of Intraretinal Layers of the Macula

Purpose

The aim of this study was to evaluate the effect of axial length (AL) on the thickness of intraretinal layers in the macula using optical coherence tomography (OCT) image analysis.

Methods

Fifty three randomly selected eyes of 53 healthy subjects were recruited for this study. The median age of the participants was 29 years (range: 6 to 67 years). AL was measured for each eye using a Lenstar LS 900 device. OCT imaging of the macula was also performed by Stratus OCT. OCTRIMA software was used to process the raw OCT scans and to determine the weighted mean thickness of 6 intraretinal layers and the total retina. Partial correlation test was performed to assess the correlation between the AL and the thickness values.

Results

Total retinal thickness showed moderate negative correlation with AL (r = -0.378, p = 0.0007), while no correlation was observed between the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCC), retinal pigment epithelium (RPE) and AL. Moderate negative correlation was observed also between the thickness of the ganglion cell layer and inner plexiform layer complex (GCL+IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) and AL which were more pronounced in the peripheral ring (r = -0.402, p = 0.004; r = -0.429, p = 0.002; r = -0.360, p = 0.01; r = -0.448, p = 0.001).

Conclusions

Our results have shown that the thickness of the nuclear layers and the total retina is correlated with AL. The reason underlying this could be the lateral stretching capability of these layers; however, further research is warranted to prove this theory. Our results suggest that the effect of AL on retinal layers should be taken into account in future studies.     

A Simple Sign for Recognizing Off–Axis OCT Measurement Beam Placement in the Context of Multicentre Studies

Purpose

Optical coherence tomography (OCT) allows quantification of the thickness of the retinal nerve fibre layer (RNFL) thickness, a potential biomarker for neurodegeneration. The estimated annual RNFL loss in multiple sclerosis amounts to 2 μm using time domain OCT. The recognition of measurement artifacts exceeding this limit is relevant for the successful use of OCT as a secondary outcome measure in clinical trials.

Methods

Prospective study design. An exploratory pilot study (ring and volume scans) followed by a cohort study (1,980 OCT ring scans). The OCT measurement beam was placed off–axis to the left, right, top and bottom of the subjects pupil and RNFL thickness of these scans were compared to the centrally placed reference scans.

Results

Off–axis placement of the OCT measurement beam resulted in significant artifacts in RNFL thickness measurements (95%CI 9μm, maximal size of error 42μm). Off–axis placement gave characteristic patterns of the OCT live images which are not necessarily saved for review. Off–axis placement also causes regional inhomogeneity of reflectivity in the outer nuclear (ONL) and outer plexiform layers (OPL) which remains visible on scans saved for review.

Conclusion

Off–axis beam placement introduces measurement artifacts at a magnitude which may mask recognition of RNFL loss due to neurodegeneration in multiple sclerosis. The resulting pattern in the OCT live image can only be recognised by the technician capturing the scans. Once the averaged scans have been aligned this pattern is lost. Retrospective identification of this artifact is however possible by presence of regional inhomogeneity of ONL/OPL reflectivity. This simple and robust sign may be considered for quality control criteria in the setting of multicentre OCT studies. The practical advice of this study is to keep the OCT image in the acquisition window horizontally aligned whenever possible.     

Clinical Factors Associated with Lamina Cribrosa Thickness in Patients with Glaucoma,as Measured with Swept Source Optical Coherence Tomography

PurposeTo investigate the influence of various risk factors on thinning of the lamina cribrosa (LC), as measured with swept-source optical coherence tomography (SS-OCT; Topcon).MethodsThis retrospective study comprised 150 eyes of 150 patients: 22 normal subjects, 28 preperimetric glaucoma (PPG) patients, and 100 open-angle glaucoma patients. Average LC thickness was determined in a 3 x 3 mm cube scan of the optic disc, over which a 4 x 4 grid of 16 points was superimposed (interpoint distance: 175 μm), centered on the circular Bruch’s membrane opening. The borders of the LC were defined as the visible limits of the LC pores. The correlation of LC thickness with Humphrey field analyzer-measured mean deviation (MD; SITA standard 24–2), circumpapillary retinal nerve fiber layer thickness (cpRNFLT), the vertical cup-to-disc (C/D) ratio, and tissue mean blur rate (MBR) was determined with Spearman''s rank correlation coefficient. The relationship of LC thickness with age, axial length, intraocular pressure (IOP), MD, the vertical C/D ratio, central corneal thickness (CCT), and tissue MBR was determined with multiple regression analysis. Average LC thickness and the correlation between LC thickness and MD were compared in patients with the glaucomatous enlargement (GE) optic disc type and those with non-GE disc types, as classified with Nicolela’s method.ResultsWe found that average LC thickness in the 16 grid points was significantly associated with overall LC thickness (r = 0.77, P < 0.001). The measurement time for this area was 12.4 ± 2.4 minutes. Average LC thickness in this area had a correlation coefficient of 0.57 with cpRNFLT (P < 0.001) and 0.46 (P < 0.001) with MD. Average LC thickness differed significantly between the groups (normal: 268 ± 23 μm, PPG: 248 ± 13 μm, OAG: 233 ± 20 μm). Multiple regression analysis showed that MD (β = 0.29, P = 0.013), vertical C/D ratio (β = -0.25, P = 0.020) and tissue MBR (β = 0.20, P = 0.034) were independent variables significantly affecting LC thickness, but age, axial length, IOP, and CCT were not. LC thickness was significantly lower in the GE patients (233.9 ± 17.3 μm) than the non-GE patients (243.6 ± 19.5 μm, P = 0.040). The correlation coefficient between MD and LC thickness was 0.58 (P < 0.001) in the GE patients and 0.39 (P = 0.013) in the non-GE patients.ConclusionCupping formation and tissue blood flow were independently correlated to LC thinning. Glaucoma patients with the GE disc type, who predominantly have large cupping, had lower LC thickness even with similar glaucoma severity.     

Optical Coherence Tomography Reveals Distinct Patterns of Retinal Damage in Neuromyelitis Optica and Multiple Sclerosis

Background

Neuromyelitis optica (NMO) and relapsing-remitting multiple sclerosis (RRMS) are difficult to differentiate solely on clinical grounds. Optical coherence tomography (OCT) studies investigating retinal changes in both diseases focused primarily on the retinal nerve fiber layer (RNFL) while rare data are available on deeper intra-retinal layers.

Objective

To detect different patterns of intra-retinal layer alterations in patients with NMO spectrum disorders (NMOSD) and RRMS with focus on the influence of a previous optic neuritis (ON).

Methods

We applied spectral-domain OCT in eyes of NMOSD patients and compared them to matched RRMS patients and healthy controls (HC). Semi-automatic intra-retinal layer segmentation was used to quantify intra-retinal layer thicknesses. In a subgroup low contrast visual acuity (LCVA) was assessed.

Results

NMOSD-, MS- and HC-groups, each comprising 17 subjects, were included in analysis. RNFL thickness was more severely reduced in NMOSD compared to MS following ON. In MS-ON eyes, RNFL thinning showed a clear temporal preponderance, whereas in NMOSD-ON eyes RNFL was more evenly reduced, resulting in a significantly lower ratio of the nasal versus temporal RNFL thickness. In comparison to HC, ganglion cell layer thickness was stronger reduced in NMOSD-ON than in MS-ON, accompanied by a more severe impairment of LCVA. The inner nuclear layer and the outer retinal layers were thicker in NMOSD-ON patients compared to NMOSD without ON and HC eyes while these differences were primarily driven by microcystic macular edema.

Conclusion

Our study supports previous findings that ON in NMOSD leads to more pronounced retinal thinning and visual function impairment than in RRMS. The different retinal damage patterns in NMOSD versus RRMS support the current notion of distinct pathomechanisms of both conditions. However, OCT is still insufficient to help with the clinically relevant differentiation of both conditions in an individual patient.     

Retinal Nerve Fiber Layer Thickness. The Beijing Eye Study 2011

Purpose

To measure retinal nerve fiber layer (RNFL) thickness in a population-based setting.

Methods

In the population-based Beijing Eye Study 2011 with 3468 individuals, RNFL thickness was measured in a subgroup of 1654 (47.7%) study participants by spectral domain optical coherence tomography (iVue SD-OCT).

Results

Mean RNFL thickness was significantly (P<0.001) higher in the inferior sector (131.4±20.6 µm) than the superior sector (126.1±19.1 µm), where it was higher than in the temporal sector (79.8±12.2 µm;P<0.001), where it was higher than in the nasal sector (75.1±12.6 µm;P<0.001). In multivariate analysis, mean global RNFL thickness (103.2±12.6 µm) increased significantly with younger age (standardized correlation coefficient beta:−0.30;P<0.001), larger neuroretinal rim area (beta:0.26;P<0.001), shorter axial length (beta:−0.21;P<0.001), thicker subfoveal choroidal thickness (beta:0.15;P<0.001), larger optic disc area (beta:0.10;P<0.001), less refractive lens power (beta:0.10;P<0.001), flatter anterior cornea (beta:0.07;P = 0.01) and female gender (beta:0.05;P = 0.03). In this population with an age of 50+ years, the age-related decline in RNFL thickness was 0.5 µm per year of life or 0.36% of an original RNFL thickness of 137 µm at baseline of the study at 50 years of age. Mean global RNFL thickness decreased by 2.4 µm for each mm enlargement of axial length.

Conclusions

The RNFL profile shows a double hump configuration with the thickest part in the inferior sector, followed by the superior sector, temporal sector and nasal sector. Factors influencing global RNFL thickness were younger age, larger neuroretinal rim, shorter axial length, thicker subfoveal choroid, larger optic disc, less refractive lens power, flatter anterior cornea and female gender. Beyond an age of 50+ years, RNFL decreased by about 0.3% per year of life at an age of 50+ years and by 2.4 µm per mm of axial elongation. These findings may be of interest for the knowledge of the normal anatomy of the eye and may be of help to diagnose diseases affecting the RNFL.     

Label-Free Density Measurements of Radial Peripapillary Capillaries in the Human Retina

Radial peripapillary capillaries (RPCs) comprise a unique network of capillary beds within the retinal nerve fibre layer (RNFL) and play a critical role in satisfying the nutritional requirements of retinal ganglion cell (RGC) axons. Understanding the topographical and morphological characteristics of these networks through in vivo techniques may improve our understanding about the role of RPCs in RGC axonal health and disease. This study utilizes a novel, non-invasive and label-free optical imaging technique, speckle variance optical coherence tomography (svOCT), for quantitatively studying RPC networks in the human retina. Six different retinal eccentricities from 16 healthy eyes were imaged using svOCT. The same eccentricities were histologically imaged in 9 healthy donor eyes with a confocal scanning laser microscope. Donor eyes were subject to perfusion-based labeling techniques prior to retinal dissection, flat mounting and visualization with the microscope. Capillary density and diameter measurements from each eccentricity in svOCT and histological images were compared. Data from svOCT images were also analysed to determine if there was a correlation between RNFL thickness and RPC density. The results are as follows: (1) The morphological characteristics of RPC networks on svOCT images are comparable to histological images; (2) With the exception of the nasal peripapillary region, there were no significant differences in RPC density measurements between svOCT and histological images; (3) Capillary diameter measurements were significantly greater in svOCT images compared to histology; (4) There is a positive correlation between RPC density and RNFL thickness. The findings in this study suggest that svOCT is a reliable modality for analyzing RPC networks in the human retina. It may therefore be a valuable tool for aiding our understanding about vasculogenic mechanisms that are involved in RGC axonopathies. Further work is required to explore the reason for some of the quantitative differences between svOCT and histology.     

Optic Nerve Diffusion Tensor Imaging after Acute Optic Neuritis Predicts Axonal and Visual Outcomes

Background

Early markers of axonal and clinical outcomes are required for early phase testing of putative neuroprotective therapies for multiple sclerosis (MS).

Objectives

To assess whether early measurement of diffusion tensor imaging (DTI) parameters (axial and radial diffusivity) within the optic nerve during and after acute demyelinating optic neuritis (ON) could predict axonal (retinal nerve fibre layer thinning and multi-focal visual evoked potential amplitude reduction) or clinical (visual acuity and visual field loss) outcomes at 6 or 12 months.

Methods

Thirty-seven patients presenting with acute, unilateral ON were studied at baseline, one, three, six and 12 months using optic nerve DTI, clinical and paraclinical markers of axonal injury and clinical visual dysfunction.

Results

Affected nerve axial diffusivity (AD) was reduced at baseline, 1 and 3 months. Reduced 1-month AD correlated with retinal nerve fibre layer (RNFL) thinning at 6 (R=0.38, p=0.04) and 12 months (R=0.437, p=0.008) and VEP amplitude loss at 6 (R=0.414, p=0.019) and 12 months (R=0.484, p=0.003). AD reduction at three months correlated with high contrast visual acuity at 6 (ρ = -0.519, p = 0.001) and 12 months (ρ = -0.414, p=0.011). The time-course for AD reduction for each patient was modelled using a quadratic regression. AD normalised after a median of 18 weeks and longer normalisation times were associated with more pronounced RNFL thinning and mfVEP amplitude loss at 12 months. Affected nerve radial diffusivity (RD) was unchanged until three months, after which time it remained elevated.

Conclusions

These results demonstrate that AD reduces during acute ON. One month AD reduction correlates with the extent of axonal loss and persistent AD reduction at 3 months predicts poorer visual outcomes. This suggests that acute ON therapies that normalise optic nerve AD by 3 months could also promote axon survival and improve visual outcomes.     

Aquaporin-2 regulates cell volume recovery via tropomyosin

Cell volume regulation is particularly important for kidney collecting duct cells. These cells are the site of water reabsorption regulated by vasopressin and aquaporin-2 (AQP2) trafficking to the apical membrane, and subject to changes in osmolality. Here, we examined the role of AQP2 in regulatory volume decrease (RVD), which is a cellular defensive process against hypotonic stress. Stable expression of AQP2 increases RVD in MDCK cells and its phosphorylation levels decrease during the RVD process. We then examined the involvement of AQP2 phosphorylation at serine 256 and serine 261 in RVD using cells stably expressing the phosphorylation mutants. Both S256A- and S256D-AQP2 decrease RVD compared to wild type (WT)-AQP2 although only S256A mutation decreases the initial osmotic swelling, indicating that AQP2-enhanced RVD is independent of osmotic swelling induced by the water permeability of AQP2. S261A and S261D mutations do not induce changes compared with WT-AQP2. These findings indicate that switching between phosphorylation and dephosphorylation at S256 is important for RVD. We previously reported that AQP2 interacts with tropomyosin 5b (TM5b), which regulates actin stability. AQP2 interactions with TM5b are rapidly increased by hypotonicity and then decreased, which are consistent with AQP2 phosphorylation levels. Knockdown and overexpression of TM5b show its essential role in WT-AQP2-enhanced RVD. RVD in S256A- and S256D-AQP2-expressing cells is not changed by TM5b knockdown or overexpression. The present study shows that AQP2 regulates RVD via TM5b and switching between phosphorylation and dephosphorylation at S256 in AQP2 is critical for this process.