Age and retinal nerve fiber layer thickness measured by spectral domain optical coherence tomography

Purpose

To evaluate the association between age and peripapillary retinal nerve fiber layer (RNFL) thickness measured by Cirrus high-definition (HD) spectral domain optical coherence tomography (OCT) in healthy Korean subjects.

Methods

A total of 302 eyes from 155 healthy Korean subjects (age range, 20 to 79 years) underwent RNFL thickness measurements using the Cirrus HD-OCT. Average, quadrant, and clock-hour RNFL thickness parameters were analyzed in terms of age using linear mixed effect models.

Results

Average RNFL demonstrated a slope of -2.1 µm per decade of age (p < 0.001). In quadrant analysis, superior (-3.4 µm/decade, p < 0.001) and inferior (-2.9 µm/decade, p < 0.001) quadrants showed steeper slopes, whereas temporal (-1.1 µm/decade, p < 0.001) and nasal (-1.0 µm/decade, p < 0.001) quadrants revealed shallower slopes. Among the 12 clock-hour sectors, clock hours 6 (-4.5 µm/decade, p < 0.001) and 1 (-4.1 µm/decade, p < 0.001) showed the greatest tendency to decline with age; RNFLs of the 3 (-0.2 µm/decade, p = 0.391) and 4 (-0.6 µm/decade, p = 0.052) o''clock hour sectors did not show significant decay.

Conclusions

RNFL thickness was associated with age, especially in superior and inferior areas. The topographic distribution of correlation between age and RNFL thickness was not uniform.     

Correlation between optic nerve head parameters and retinal nerve fibre layer thickness measured by spectral-domain optical coherence tomography in myopic eyes

Background: To evaluate the correlation between optic nerve head parameters and retinal nerve fiber layer thickness measured by Cirrus HD spectral‐domain optical coherence tomography (Cirrus HD‐OCT; Carl Zeiss Meditec) in healthy myopic eyes. Design: Cross‐sectional study. Participants: One hundred and sixty‐one right eyes from 161 healthy young myopic subjects. Methods: Optic nerve head parameters and retinal nerve fiber layer thickness were measured with the Cirrus HD‐OCT. The distance between optic disc margin and scan circle (disc margin‐to‐scan distance) was measured on the Cirrus HD‐OCT en‐face optic nerve head image with aid of National Institutes of Health ImageJ image‐analysis software (developed by Wayne Rasbands, National Institutes of Health, Bethesda, MD). Main Outcome Measures: The correlations among optic nerve head parameters, retinal nerve fibre layer thickness and the disc margin‐to‐scan distance were evaluated with and without adjustment of the magnification effect. Results: Without correction of the magnification effect, the thicker average retinal nerve fiber layer was correlated with greater rim area and lower degree of myopia (P < 0.001). When the magnification effect was corrected, thicker average retinal nerve fibre layer was associated with greater disc area and greater rim area in univariate and multivariate analyses (P ≤ 0.028); however, degrees of myopia and the disc margin‐to‐scan distance were not significantly associated with average RNFL thickness (P ≥ 0.104). Conclusions: Thicker average retinal nerve fibre layer thickness was associated with greater rim and disc areas. Disc margin‐to‐scan distance was not significantly correlated with average retinal nerve fibre layer thickness in healthy myopic eyes.     

The relationship between the optical density of cataract and its influence on retinal nerve fibre layer thickness measured with spectral domain optical coherence tomography

Purpose: The purpose of this study was to model the influence of cataract on Spectral Domain Optical Coherence Tomography (SDOCT) image quality and Retinal Nerve Fibre Layer (RNFL) thickness measurements. Methods: SDOCT images, made with two different devices (3DOCT‐1000, Topcon and Cirrus HD‐OCT), before and after cataract surgery were compared and judged against measurements from normal subjects using artificial filters simulating the effects of cataract. Optical density of the images was calculated based on a mathematical model described previously. Results: In total, forty‐eight eyes were included for pre‐ and postoperative cataract extraction measurements. OCT image quality significantly (p < 0.001) improved postoperative and postoperative RNFL thickness was significantly (p < 0.001) thicker in both groups of patients. The measurements using artificial filters showed a rather precise linear relation between change in filter induced optical density and change in RNFL thickness (R = 0.941, p < 0.001 for 3DOCT‐1000 and R = 0.785, p < 0.001 for Cirrus HD‐OCT). For the patient groups, the relation was less marked, 3DOCT‐1000 R_s = 0.697, p < 0.03 and Cirrus HD‐OCT R_s = 0.444, p < 0.03. The predictive potential based on the found linear relationship between OCT‐effective optical density of cataract and the cataract‐induced underestimation was however limited, and mean difference ± SD between predicted and measured RNFL thickness were 1.68 ± 7.55 (3DOCT‐1000) and 3.71 ± 2.97 (Cirrus HD‐OCT) micron. Conclusions: A linear relationship exists between OCT‐effective optical density of cataract and underestimation of RNFL thickness measured with OCT. This finding holds promise to correct for cataract‐induced changes in RNFL measurements, but will differ for each type of OCT device.     

Cirrus HD OCT检测近视眼视网膜神经纤维层厚度的研究

目的：应用Cirrus HD OCT检测近视眼视网膜神纤维层厚度,探讨近视眼神经纤维层厚度分布特点及其与屈光度的关系。 方法：将近视眼106例196眼分为低、中、高度近视组和正常对照组38例60眼,应用Cirrus HD OCT进行以视盘为中心,直径3.46 mm圆周的RNFL厚度测量,计算各组平均、各象限及各钟点RNFL厚度,各近视组分别与正常对照组对比,研究近视眼RNFL厚度与屈光度的关系。 结果：各近视组平均、上方象限及下方象限RNFL厚度较正常对照组变薄,其中中度、高度近视与正常对照组相比有统计学差异（ P〈0.05）,鼻侧象限RNFL厚度变薄,无统计学显著性差异（ P〉0.05）,颞侧象限RNFL厚度增加,有统计学差异（ P〈0.05）;各近视组2：00,6：00,12：00位RNFL厚度较正常对照组变薄,有统计学差异（ P〈0.05）,8：00,9：00,10：00位RNFL厚度较正常对照组增加,有统计学差异（ P〈0.05）,中、高度近视1：00,5：00位厚度较正常对照组变薄,有统计学差异（P〈0.05）。 结论：近视眼平均、上方及下方象限、2：00,6：00,12：00位RNFL厚度较正常对照组变薄,颞侧象限、8：00,9：00,10：00位RNFL厚度较正常对照组相比明显增加,这是近视眼RNFL厚度的特点,当临床出现RNFL厚度异常时,应考虑屈光度的影响,综合评价其临床意义;近视眼7：00,8：00,10：00,11：00位RNFL厚度与正常对照组相比均未变薄,出现异常变薄时,应考虑青光眼可能。     

近视性屈光参差性弱视患者视网膜黄斑中心凹及神经纤维层厚度的研究

背景弱视是一种从视网膜到视中枢的视觉传导系统及中枢全领域形态学及功能异常引起的临床表现,目前弱视眼的视网膜是否受累仍是争论的焦点。目的采用光学相干断层扫描（OCT）测量单眼近视性屈光参差性弱视患者的视网膜黄斑中心凹厚度及视网膜神经纤维层（RNFL）厚度,探讨单眼近视性屈光参差性弱视患者视网膜是否存在组织病理学改变。方法取近视性屈光参差性弱视患者22例44眼为弱视组;近视性屈光参差性弱视患者经治疗后视力达到正常者10例20眼为弱视治愈组;初诊为近视性屈光参差非弱视患者11例22眼为非弱视组。所有患者采用Model3000型OCT测量双眼视网膜黄斑中心凹厚度及视盘周围RNFL厚度,包括上方、下方、鼻侧、颞侧和平均厚度。采用配对t检验对各组受试者双眼间视网膜厚度的差异进行比较,用多元线性回归方法分析黄斑中心凹视网膜厚度及RNFL厚度与弱视眼眼轴长度、屈光度和年龄的关系。结果弱视组患者中弱视眼黄斑中心凹厚度明显比对侧眼增厚,差异有统计学意义（P=0．001）;弱视治愈组原弱视眼与对侧眼之间视网膜厚度的差异无统计学意义（P=0．778）,非弱视组高度数近视眼与低度数近视眼之间视网膜厚度的差异无统计学意义（P=0．943）;弱视组弱视眼颞侧RNFL厚度明显比对侧眼增厚,差异有统计学意义（P〈0．001）,弱视治愈组原弱视眼颞侧RNFL厚度比对侧眼厚,差异有统计学意义（P=0．003）,非弱视组高度数眼颞侧RNFL厚度比低度数眼厚,差异有统计学意义（P=0．046）,各组双眼视网膜上方、下方、颞侧及平均RNFL厚度的差异均无统计学意义（P〉0．05）。年龄与视盘下方RNFL厚度间呈负相关关系（r=-0．559,P=0．016）,其余各参数之间均无明显相关（P〉0．05）。结论近视性屈光参差性弱视患者的黄斑中心凹视网膜较正常眼增厚,而RNFL厚度与一般近视眼无明显差别;弱视的改善伴随着黄斑中心凹厚度的减小。     

Stratus相干光断层扫描仪测量正常人视网膜神经纤维层的厚度

目的建立Stratus OCT测量我国正常人视网膜神经纤维层(RNFL)厚度的正常值,探讨正常人RNFL厚度的变异程度和与年龄及性别的关系。设计前瞻性横断面研究。研究对象10～69岁的正常人。方法用Stratus OCT的扫描程序(Fast RNFL Thickness 3.4)对210例(210眼)正常人进行视乳头环形扫描,测量各象限和平均RNFL厚度值,应用SPSS 11.5软件统计学处理。主要指标RNFL厚度值。结果210例正常人上方象限、颞侧象限、下方象限、鼻侧象限及全周平均的RNFL厚度分别为(145.5±16.8)、(84.2±12.8)、(147.6±15.2)、(84.7±14.2)μm。平均RNFL厚度变异最小,鼻侧RNFL厚度变异最大。除鼻侧象限外,其它各象限及平均RNFL厚度与年龄均呈负相关性。对正常人RNFL厚度无性别差异。结论用Stratus OCT测量的正常人RNFL厚度数值中,平均RNFL厚度变异最小,鼻侧RNFL厚度变异最大;RNFL厚度随年龄增长而变薄。     

相干光断层扫描仪检测视网膜神经纤维层厚度影响因素分析

目的运用相干光断层扫描仪(OCT)测量正常人视网膜神经纤维层(RNFL)厚度并探讨其影响因素。方法运有Stratus OCT 4.0测量202例不同年龄及不同屈光度正常人(年龄8～74岁,屈光度-8～ 4D)各钟点、象限及平均RNEL厚度,建立多元线性回归方程探讨年龄、屈光度、性别及视盘面积对RNEL厚度的影响。结果①正常人RNFL平均厚度为108.63±9.70μm,下方象限RNFL(I):139.17±15.79μm最厚,其次为上方象限(S):134.61±17.80μm,颞侧象限(T):85.37±21.25μm,鼻侧象限(N):75.19±17.06μm最薄,即I>S>T>N。②平均及上、下、颞侧象限RNFL厚度均随年龄增长而变薄,40岁以后趋势明显,50岁以上者显著变薄,仅鼻侧象限RNFL厚度与年龄无关;平均及上、下、鼻侧象限RNFL厚度均随近视度数增加而变薄,且高度近视者显著薄于正视者。而颞侧象限RNFL厚度却随近视度数增加而变厚,高度近视者显著薄于正视者。而颞侧象限RNFL厚度却随近视度数增加而变厚,高度近视者显著厚于正视者;平均及各象限RNFL厚度除下方外均与性别无关,仅下方像限女性较男性厚;应用机器自动辨认视盘边界时,未发现RNFL厚度与视盘面积有关。结论OCT测得的正常RNFL厚度主要与年龄、屈光度有关;仅下方象限RNFL厚度与性别有关;应用机器自动辨认视盘边界时,未发现RNFL厚度与视盘面积有关;儿童可以较好地配合OCT检查并获得较为可靠的测理结果;应用规范、统一的OCT测量标准,建立人群为基础的并经相关影响因素校正的中国人RNFLJE常值数据库对青光眼的早期诊断是非常必要的。     

The effect of various factors on variability of retinal nerve fiber layer thickness measurements using optical coherence tomography

Purpose

To evaluate the effects of various factors on the variability of retinal nerve fiber layer (RNFL) thickness measurements using the Stratus optical coherence tomography (OCT) in normal and glaucomatous eyes.

Methods

Four hundred seventy-four subjects (103 normal eyes and 371 glaucomatous eyes) were scanned to determine the RNFL thickness measurements using the Stratus OCT. Measurements were obtained twice during the same day. The standard deviation (SD) was used to compare the variability in RNFL thickness measurements of the normal subjects to that of the glaucomatous patients. Multivariate regression analysis was used to evaluate which covariates were independent predictors of SD in overall mean RNFL thickness.

Results

The mean SD of all RNFL thickness measurements was larger in the glaucoma group except in one sector. In the multivariate regression analysis, the average signal strength (SS) and the relative SS change (difference in SS between initial and repeat scans, divided by initial SS) were independent predictors of the SD in the RNFL thickness measurements (partial R² = 0.018, 0.013; p = 0.016, 0.040, respectively).

Conclusions

Glaucomatous eyes tend to be more variable than normal eyes in RNFL thickness measurement using the Straus OCT. The average SS and the relative SS changes appear to correlate with the variability in RNFL thickness measurement. Therefore, the results of the RNFL analysis should not be interpreted independently of these factors.     

Comparison of two retinal nerve fibre layer thickness measurement patterns of RTvue optical coherence tomography

Background: To evaluate the agreement and repeatability between operator‐dependent centring and automatic centring retinal nerve fibre layer thickness measurement patterns (RNFL3.45 and NHM4) of RTvue optical coherence tomography in normal and glaucomatous eyes. Design: Cross‐sectional observational study. Participants: A total of 153 eyes from 149 normal subjects and subjects with glaucoma were analysed. Methods: The retinal nerve fibre layer thickness was measured using RNFL3.45 and NHM4 three times on the same day to determine the repeatability and agreement between the two scan patterns. Main Outcome Measures: Student's paired t‐testing, intra‐class correlation coefficient, coefficient of variation, test–retest viability, Pearson's correlation coefficient and Bland–Altman analysis of retinal nerve fibre layer thickness measurements. Results: The difference between RNFL3.45 and NHM4 measurements was statistically significant by paired t‐testing (P = 0.003) only in severe glaucoma group. The Pearson's correlation test showed a high degree of correlation of the mean retinal nerve fibre layer thickness (r = 0.949). Bland–Altman plots showed that the differences between RNFL3.45 and NHM4 were smaller at thicker retinal nerve fibre layer values, but larger at thinner retinal nerve fibre layer values. The intra‐class correlation coefficient for RNFL3.45 (and lower 95% confidence interval) in normal and glaucomatous eyes was 0.990 (0.985 confidence interval) and 0.997 (0.995 confidence interval), respectively. The intra‐class correlation coefficient for NHM4 in normal and glaucomatous eyes was 0.989 (0.983 confidence interval) and 0.995 (0.992 confidence interval), respectively. The test–retest variability for RNFL3.45 and NHM4 ranged from 3.98 to 9.75 µm in normal eyes, and from 4.10 to 13.34 µm in glaucomatous eyes. Conclusion: Measurements of retinal nerve fibre layer thickness by RNFL3.45 and NHM4 are in good agreement.     

光学相干断层成像与组织形态学检测猴青光眼视网膜神经纤维层厚度的比较

目的应用光学相干断层成像术（optical coherence tomography,OCT）检测活体青光眼视网膜神经纤维层（retinal nerve fiber layer,RNFL）厚度,并与组织形态学检测结果进行比较。方法选用Cynomolgus猴4只眼,通过氩激光烧灼小梁网,引起眼压升高,制作成青光眼动物模型。应用OCT测量视盘周围直径,选取直径为2.4mmRNFL厚度的猴眼进行研究。在完成最后一次OCT测量后,将眼球摘除。摘除的眼球置于10％甲醛液中固定,石蜡包埋做连续切片及HE染色。应用与光学显微镜相联接的计算机图像处理系统,测量与OCT扫描相对应点的组织学切片的RNFL厚度。结果OCT测量RNFL平均厚度为（72.2±54.5）μm;组织形态学测量RNFL平均厚度为（70.3±51.1）μm,未经校正的组织形态学测量平均厚度为（61.1±44.2）μm。两种检测结果差异无显著性（t=1.895,P＞0.05）。结论OCT活体测量RNFL的平均厚度与组织形态学测量结果基本相同,但OCT活体测量RNFL厚度值与经校正后的组织形态学测量结果更接近。     

Nerve fibre layer changes in highly myopic eyes by optical coherence tomography

Objective: The purpose of this study was to investigate any correlations that may exist between retinal nerve fibre layer (RNFL) thickness and high myopia by optical coherence tomography (OCT).Design: Case-control study.Participants: Ten patients (20 eyes) with high myopia and 10 control patients (20 eyes) matched for age and sex were recruited from a database search of 1 vitreoretinal practice in Regina, Sask.Methods: The RNFL thickness of 10 highly myopic patients and 10 control patients matched for age and sex from a clinical practice was determined using the Stratus OCT. All 10 highly myopic patients selected for the study had a spherical equivalent of ≥−10.0 D OU and an intraocular pressure <21 mm Hg OU, and failed to display glaucomatous changes such as disc hemorrhages and glaucomatous cupping in either eye. None of the patients included in the study had evidence of concomitant ophthalmic disease and none had had previous refractive surgery. Axial length measurements were done on all patients using the IOL Master.Results: The mean (SD) RNFL thicknesses in the control and myopic groups were 108.8 (10.6) μm and 80.0 (18.6) μm, respectively, with t = 6.0 and p − 0.001. A negative correlation of −0.712 with p < 0.001 was found between RNFL thickness and axial length.Conclusions: When interpreting the RNFL thickness of highly myopic patients by OCT, careful attention must be given to the inherently thinner RNFL to avoid a false glaucoma diagnosis.     

白内障对 OCT视网膜神经纤维层厚度测量影响的初步分析

目的：探讨白内障混浊程度对相干光断层扫描（ OCT）进行视网膜神经纤维层（ RNFL）厚度测量的影响。方法根据Emery晶状体核硬度分级标准,将核型年龄相关性白内障患者分为Ⅱ级核、Ⅲ级核、Ⅳ级核组,每组入选20只眼,分析白内障术前术后RNFL厚度测量值的差异与晶状体密度值的相关性。结果晶状体密度值每两组之间差异具有统计学意义（ P ＜0．05）。随着晶状体核混浊程度加重,晶状体密度值逐渐增加。各组间术后RNFL厚度测量值在上象限、下象限及全周平均值分别对比均无统计学意义（ P ＞0．05）。Ⅱ级核组无论上象限、下象限还是全周平均RNFL厚度测量值,手术前后分别对比均无明显差异（ P ＞0．05）。Ⅲ级核组上象限、下象限、全周平均RNFL厚度测量值术前术后分别对比具有差异性（ P ＜0．05）,其晶状体密度值与差异值均具有线性正相关（上象限r ＝0．654, P ＜0．05,下象限r ＝0．636, P ＜0．05,全周平均值r ＝0．661, P ＜0．05）。Ⅳ级核组手术前后上象限、全周平均RNFL厚度测量值具有显著性差异（ P ＜0．01）,下象限RNFL厚度测量值同样具有差异性（ P＜0．05）。晶状体密度值与RNFL术前术后差异值在下象限、全周平均值具有显著线性正相关（下象限r ＝0．811, P ＜0．01,全周平均值r ＝0．777, P ＜0．01）,在上象限具有相关性（ r ＝0．713, P ＜0．05）。结论当晶状体核混浊达到Ⅲ级以上程度时,OCT测量RNFL厚度结果可能出现误差,不能准确反映RNFL真实厚度。     

Glaucomatous retinal nerve fibre layer defects may be identified in Stratus OCT images classified as normal

Purpose: We aimed to compare the retinal nerve fibre layer (RNFL) in different Stratus optical coherence tomography (OCT) images in glaucoma eyes with RNFL thickness values within normal limits. Methods: We studied the Stratus OCT high‐resolution standard protocol for assessment of peripapillary RNFL thickness. The four glaucoma eyes presented (with reproducible visual field defects, mean deviations from ? 3.49 dB to ? 0.49 dB and structural loss on RNFL and/or disc photography) had results within the 95% normal limits for all OCT parameters (full circle, quadrant or clock hour mean RNFL thickness). We qualitatively compared the RNFL in pseudo‐colour and grey‐scale images defined by the Stratus OCT software with what appeared to be the RNFL when not defined automatically (and in raw data OCT images). Results: A localized RNFL defect was identified in conventional 495‐nm RNFL photographs in all four patients. Obviously, in these selected eyes, the atrophy was not picked up by the OCT RNFL border algorithm, and at the corresponding location a localized RNFL atrophy (narrowing of the high signal intensity RNFL) was either not or just barely detectable in pseudo‐colour OCT. However, defects seemed to be present in OCT grey‐scale and raw data images in all four eyes. Conclusions: Our observations suggest that OCT images obtained in glaucoma eyes that are misclassified by the standard statistical analyses of Stratus OCT may contain information indicating RNFL defects. Thus, the current diagnostic ability of OCT in glaucoma can probably be extended.     

Correlation between retinal nerve fibre layer thickness and retinal sensitivity

Purpose: To evaluate the relationship between retinal nerve fibre layer (RNFL) thickness measured by optical coherence tomography (OCT) and light threshold values obtained with the Micro Perimeter 1 (MP1). Methods: Forty‐nine normal subjects and 37 glaucoma patients were included. Thickness of the RNFL around the optic disc was measured with Stratus OCT scans, and static threshold perimetry was performed with the MP1 at the same visit. Total average and mean 12‐clock‐hour RNFL thickness were measured with Stratus OCT. An automated 4‐2‐1 staircase strategy with Goldmann III stimuli was used for MP1. The correspondence between Stratus OCT and MP1 RNFL measurements in each clock‐hour was best fit by a second‐order polynomial. Results: Average RNFL thickness in the normal group was significantly higher than that in the glaucoma group in each clock hour. Comparing the normal and glaucomatous groups, retinal sensitivity differed significantly at 6, 7, 8 and 11 o’clock. In these regions, structure–function relationships were generally stronger than in other regions. Conclusions: Structure–function associations may be strong when loss of nerve fibres is severe. However, significant reduction in retinal sensitivity does not emerge until the atrophy of nerve fibres is severe.     

Machine learning classifiers for glaucoma diagnosis based on classification of retinal nerve fibre layer thickness parameters measured by Stratus OCT

Purpose: To compare the performance of two machine learning classifiers (MLCs), artificial neural networks (ANNs) and support vector machines (SVMs), with input based on retinal nerve fibre layer thickness (RNFLT) measurements by optical coherence tomography (OCT), on the diagnosis of glaucoma, and to assess the effects of different input parameters. Methods: We analysed Stratus OCT data from 90 healthy persons and 62 glaucoma patients. Performance of MLCs was compared using conventional OCT RNFLT parameters plus novel parameters such as minimum RNFLT values, 10th and 90th percentiles of measured RNFLT, and transformations of A‐scan measurements. For each input parameter and MLC, the area under the receiver operating characteristic curve (AROC) was calculated. Results: There were no statistically significant differences between ANNs and SVMs. The best AROCs for both ANN (0.982, 95%CI: 0.966–0.999) and SVM (0.989, 95% CI: 0.979–1.0) were based on input of transformed A‐scan measurements. Our SVM trained on this input performed better than ANNs or SVMs trained on any of the single RNFLT parameters (p ≤ 0.038). The performance of ANNs and SVMs trained on minimum thickness values and the 10th and 90th percentiles were at least as good as ANNs and SVMs with input based on the conventional RNFLT parameters. Conclusion: No differences between ANN and SVM were observed in this study. Both MLCs performed very well, with similar diagnostic performance. Input parameters have a larger impact on diagnostic performance than the type of machine classifier. Our results suggest that parameters based on transformed A‐scan thickness measurements of the RNFL processed by machine classifiers can improve OCT‐based glaucoma diagnosis.