Progressive Retinal Nerve Fiber Layer Thinning Research Articles

Trend-Based Progression Analysis for Examination of the Topography of Rates of Retinal Nerve Fiber Layer Thinning in Glaucoma

Measurement of the rates of retinal nerve fiber layer (RNFL) thinning has consisted primarily of the circumpapillary RNFL profile. This study reports the rates of RNFL thinning over the 6 × 6 mm2 RNFL thickness map and their application for indication of visual field (VF) worsening in patients with glaucoma. To investigate the association between the rates of RNFL thinning and the risk of VF worsening in patients with glaucoma. This prospective study included 117 eyes of 89 Chinese patients with primary open-angle glaucoma followed up at approximate 4-month intervals for 5 or more years between July 1, 2007, and October 30, 2015, with progressive RNFL thinning detected by optical coherence tomography trend-based progression analysis (TPA). The mean and the peak rates of RNFL thinning and the area of progressive RNFL thinning were measured by the rates of change of RNFL thickness map. Visual field worsening was determined by the Early Manifest Glaucoma Trial and pointwise linear regression criteria. Hazard ratios (HRs) for indication of VF worsening determined by time-varying Weibull survival models. Of 89 patients (117 eyes) included in the study, 53 (59.6%) were men; mean (SD) age was 54.0 (13.8) years. At the time that progressive RNFL thinning was confirmed by TPA, the mean and the peak rates of RNFL thinning were 9.06 (8.05) µm/y and 4.52 (3.19) µm/y, respectively, and the area of progressive RNFL thinning was 1.54 (1.83) mm2. The inferotemporal meridians at 268° to 288° and the superotemporal meridians at 40° to 60° were the most frequent locations where progressive RNFL thinning was observed; 41.9% of the eyes had progressive RNFL thinning at these locations. After controlling for baseline covariates, the peak and the mean rates of RNFL thinning, but not the area of progressive RNFL thinning, were indicative of VF worsening. For each micrometer-per-year increase in the peak and the mean rates of RNFL thinning, the hazard ratios were 1.12 (95% CI, 1.04-1.19) for the peak rate and 1.39 (95% CI, 1.19-1.62) for the mean rate by the Early Manifest Glaucoma Trial criteria, and 1.07 (95% CI, 1.03-1.10) for the peak rate and 1.18 (95% CI, 1.09-1.28) for the mean rate by the pointwise linear regression criteria. Topographic measurement of the rates of RNFL thinning by optical coherence tomography TPA is informative for risk assessment of VF loss in glaucoma. Although progressive RNFL thinning may not necessarily be associated with VF worsening, faster rates of RNFL thinning were associated with a higher risk of subsequent decline in VF.

Peripapillary RNFL Thickness Changes after Panretinal Photocoagulation

To evaluate changes in peripapillary retinal nerve fiber layer (RNFL) thickness as determined by spectral domain optical coherence tomography (SD-OCT) after panretinal photocoagulation (PRP) for proliferative diabetic retinopathy (PDR). Forty-two eyes of 42 diabetic patients who were scheduled for PRP were enrolled in this interventional case series. Peripapillary RNFL thickness was measured using SD-OCT (OCT 1000; Topcon Co., Tokyo, Japan) at baseline and 1, 3, and 6 months after PRP. Mean global RNFL thickness was increased significantly by 3 μm (p = 0.04) 1 month after PRP and was then decreased marginally significantly by 2.4 μm at 6 months (p = 0.054) as compared to baseline values. After 1 month, RNFL thickness was increased in all quadrants, but only changes in the temporal quadrant were significant (p = 0.009). At 6 months, progressive RNFL thinning occurred in all quadrants; however, only changes in the superior quadrant were significant (p = 0.041). Visual acuity was improved by an average of 0.02 logMAR after 6 months, but this change was not statistically significant. Shortly after PRP, RNFL thickness (as determined by SD-OCT) increases, but a decrease in RNFL thickness occurs at 6 months post-PRP. RNFL thickness changes based on OCT should be interpreted with caution in diabetic eyes undergoing PRP.

Risk of Visual Field Progression in Glaucoma Patients with Progressive Retinal Nerve Fiber Layer Thinning: A 5-Year Prospective Study

To investigate whether progressive retinal nerve fiber layer (RNFL) thinning is predictive of progressive visual field (VF) loss in glaucoma. Prospective study. A total of 139 primary open-angle glaucoma patients (240 eyes) followed up for ≥5 years. Retinal nerve fiber layer imaging and VF testing were performed at ∼4-month intervals. Progressive RNFL thinning was determined by event analysis (Guided Progression Analysis [GPA]) and trend analysis (Trend-based Progression Analysis [TPA]) of serial registered RNFL thickness maps. VF progression was detected according to the Early Manifest Glaucoma Trial (EMGT) ("likely progression") and pointwise linear regression (PLR) criteria (≥3 contiguous locations with sensitivity change <0 decibels [dB]/year at P < 0.01). Hazard ratios (HRs) for predicting VF progression were calculated by Cox proportional hazard modeling with progressive RNFL thinning as a time-dependent covariate. The specificity of GPA/TPA for detection of RNFL changes was determined by the proportion of eyes with significant RNFL thinning/thickening in 25 normal subjects followed weekly for 8 consecutive weeks and the proportion with significant RNFL thickening in the glaucoma group. The HRs of VF progression. A total of 65 (27.1%) and 117 eyes (48.8%) had progressive RNFL thinning based on GPA and TPA, respectively, and 30 (12.5%) and 39 eyes (16.3%) had VF progression per the EMGT and PLR criteria, respectively, during follow-up. Eyes with progressive RNFL thinning had lower VF survival estimates and a faster decline of visual field index than eyes without. Progressive RNFL thinning predicted the development of VF progression with HRs of 8.44 (95% confidence interval, 3.30-21.61) (EMGT criteria) and 5.11 (2.51-10.42) (PLR criteria) for TPA and 3.95 (1.74-8.93) (EMGT criteria) and 3.81 (1.83-7.92) (PLR criteria) for GPA after controlling for baseline covariates. The specificities of GPA and TPA were 100% (83.4%-100.0%) in the normal group and 81.7% (76.2%-86.4%) and 84.2% (78.9%-88.6%), respectively, in the glaucoma group. Progressive RNFL thinning determined by GPA and TPA is predictive of detectable functional decline in glaucoma. This finding underscores the significance of detecting progressive RNFL thinning and itsrelevance to initiate or augment treatment for glaucoma patients. Regulatory authorities may consider progressive RNFL thinning as an outcome measure in clinical trials for evaluation of glaucoma treatment.

Lamina Cribrosa Reversal after Trabeculectomy and the Rate of Progressive Retinal Nerve Fiber Layer Thinning

To determine whether the reversal of lamina cribrosa (LC) displacement observed after trabeculectomy is associated with the rate of progressive retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG). Observational case series. Thirty-four patients with POAG who underwent trabeculectomy and were followed up for at least 2.5 years, during which the RNFL thickness was measured by serial spectral-domain (SD) optical coherence tomography (OCT). The participants underwent enhanced depth imaging scanning of the optic nerve using SD OCT before surgery (PREOP), at a 6-month postoperative follow-up (FU1), and at a subsequent follow-up that was performed at least 2.5 years postoperatively (FU2), and serial RNFL thickness was measured at least 5 times during the study period. Preoperative and postoperative LC depths (LCDs) as determined on 7 selected B-scan images from each eye were averaged to produce the mean LCD. The rate of RNFL thinning was determined by linear regression of serial OCT RNFL thickness measurements over time. Factors associated with the rate of OCT RNFL thinning. The intraocular pressure (IOP) decreased from 23.8±7.9 mmHg (mean±standard deviation) to 11.0±4.4 mmHg at FU1 (P<0.001) and subsequently increased to 13.1±5.2 mmHg at an overall follow-up of 3.5±0.8 years (P=0.003). The LCD was reduced from 589.90±148.32 to 508.57±136.28 μm at FU1 (P<0.001). A subsequent slight but nonsignificant increase in the LCD was noted at FU2 (516.48±145.87 μm; P=0.410). A faster rate of RNFL thinning was associated with a shorter follow-up period (P=0.032), higher IOP at PREOP (P=0.011) and FU2 (P=0.014), and a larger increase in LCD from FU1 to FU2 (P<0.001). The changes in LCD between PREOP and FU1 and between PREOP and FU2 were not associated with the rate of RNFL thinning. Eyes with sustained LCD reduction over a long period had a slow rate of progressive RNFL thinning after trabeculectomy. A large LCD reduction in the early postoperative period was not associated with the long-term rate of progression if it was not maintained during subsequent follow-up.

Influence of Lamina Cribrosa Thickness and Depth on the Rate of Progressive Retinal Nerve Fiber Layer Thinning

To determine whether lamina cribrosa (LC) depth (LCD) and LC thickness (LCT) are associated with a faster rate of progressive retinal nerve fiber layer (RNFL) thinning in primary open-angle glaucoma (POAG). Prospective, observational study. One hundred ten eyes diagnosed with POAG (n = 110 patients) in which RNFL thickness had been measured by serial spectral-domain (SD) optical coherence tomography (OCT) for at least 2.5 years. The participants underwent enhanced depth imaging volume scanning of the optic nerve, and circumpapillary RNFL thickness measurements were obtained using SD OCT. The participants were followed up regularly with serial RNFL thickness measurements at 6-month or longer intervals. Lamina cribrosa depth was measured at 7 equidistant planes and LCT was measured at 3 locations (superior midperipheral, midhorizontal, and inferior midperipheral). The rate of RNFL thinning was determined by linear regression of serial OCT RNFL thickness measurements over time. Factors associated with the rate of OCT RNFL thinning. A faster rate of RNFL thinning was associated with disc hemorrhage during follow-up (P < 0.001), wider β-zone parapapillary atrophy with Bruch's membrane (P = 0.037), larger global RNFL thickness (P = 0.026), larger LCD (P < 0.001), and smaller LCT (P = 0.002). The association between LCD and the rate of RNFL thinning was explained better using a fractional polynomial model (R(2) = 0.223) than a linear model (R(2) = 0.134; P = 0.010). Davies' test revealed a statistically significant breakpoint for LCD (489.7 μm), above which a faster rate of global RNFL thinning was associated with a larger LCD. A thinner LC and a larger LC displacement had a significant influence on the rate of progressive RNFL thinning.

Diagnosing glaucoma progression with optical coherence tomography

Optical coherence tomography (OCT) imaging of the retinal nerve fiber layer (RNFL), optic nerve head (ONH) and macula has gained popularity in recent years to detect and monitor glaucoma. With significant improvement in scan speed and scan resolution, spectral-domain OCT has become an efficient platform to evaluate progressive RNFL thinning and ONH remodeling. This review summarizes the recent progress of OCT RNFL, ONH and macular measurements for the detection of glaucoma progression. The RNFL thickness map facilitates visualization of RNFL defects and their progression patterns, and attains a higher sensitivity to detect glaucoma progression compared with the conventional circumpapillary RNFL thickness profile. The measurement of lamina cribrosa displacement is informative to discern the relationship between intraocular pressure and ONH modeling. Ganglion cell and inner plexiform layer analysis has offered a useful alternative to track glaucoma progression. In the interpretation of progression analysis, the impact of age-related change, disease severity and image signal-to-noise ratio should always be considered. The analyses of the RNFL thickness map, lamina cribrosa displacement and inner macular thickness have provided a new paradigm to evaluate glaucomatous damage and its progression.

Microstructure of β-Zone Parapapillary Atrophy and Rate of Retinal Nerve Fiber Layer Thinning in Primary Open-Angle Glaucoma

To investigate whether the rate of retinal nerve fiber layer (RNFL) thinning differs according to the microstructure of β-zone parapapillary atrophy (PPA) as evaluated by spectral-domain (SD) optical coherence tomography (OCT) in primary open-angle glaucoma (POAG). Prospective, observational, comparative study. A total of 195 eyes with POAG that had been evaluated by serial SD-OCT RNFL thickness measurements for ≥ 2 years. On the basis of the extent of Bruch's membrane (BM) within the β-zone PPA (area without retinal pigment epithelium [RPE]), as shown in the infrared fundus images, PPA was divided into PPA+BM (PPA with intact BM) and PPA-BM (PPA devoid of BM). Eyes were categorized into group A (having PPA+BM only, n=64), group B (having both PPA+BM and PPA-BM, n=58), group C (having PPA-BM only, n=32), and group D (without β-zone PPA, n=41). The rate of progressive OCT RNFL thinning was determined by linear regression and compared between groups. Factors influencing the rate of RNFL thinning were evaluated, including age, sex, follow-up duration, history of filtering surgery, baseline RNFL thickness, baseline intraocular pressure (IOP), mean IOP and IOP fluctuation during follow-up, PPA types, baseline PPA width, PPA width increase, axial length (AXL), central corneal thickness, and visual field mean deviation (MD). Rate of thinning of OCT RNFL thicknesses over time. Patients in groups B and C were significantly younger and more myopic, and had a greater AXL, than those in groups A and D (all P<0.001). The rate of global RNFL thinning was significantly faster in group A (-1.66 ± 2.94 μm/year) than in the other groups (group B, -0.87 ± 1.28 μm/year; group C, 0.20 ± 1.86 μm/year; group D, -0.28 ± 1.74 μm/year; P = 0.001). Multivariate regression showed a significant association of shorter follow-up period (P = 0.016), greater baseline global RNFL thickness (P = 0.035), type of β-zone PPA (group A, P = 0.023), and greater baseline PPA+BM width (P = 0.034) with a faster rate of RNFL thinning. The rate of RNFL thinning differed according to the microstructure of β-zone PPA. It was faster for eyes with β-zone PPA with intact BM than for eyes without β-zone PPA or with β-zone PPA devoid of BM.

Retinal Nerve Fiber Layer Progression in Glaucoma: A Comparison between Retinal Nerve Fiber Layer Thickness and Retardance

To investigate the performance of spectral-domain optical coherence tomography (OCT) and scanning laser polarimetry to detect progressive retinal nerve fiber layer (RNFL) changes and to determine whether reduction of the RNFL retardance occurred before thinning of the RNFL in glaucoma. Prospective, longitudinal study. One hundred eighty-four eyes of 116 glaucoma patients and 43 normal eyes of 23 healthy individuals. Patients were followed up every 4 months for at least 36 months with RNFL retardance (GDx Enhanced Corneal Compensation; Carl Zeiss Meditec) and RNFL thickness (Cirrus HD-OCT; Carl Zeiss Meditec) measured in the same visit. Progressive RNFL retardance and thickness changes were evaluated with event-based analysis (Guided Progression Analysis; Carl Zeiss Meditec) with reference to the RNFL retardance change map and the RNFL thickness change map, respectively. The area and frequency distribution of RNFL changes were examined by overlaying the RNFL retardance change maps and the RNFL thickness change maps in the latest follow-up. The agreement of RNFL retardance and RNFL thickness progression was evaluated with κ statistics. Number of eyes with progressive RNFL changes over time. A total of 2472 OCT thickness maps and 2472 RNFL retardance maps were collected and reviewed with a mean follow-up of 55.1 months. Twenty-seven eyes (14.6%; 26 glaucoma patients) showed progressive RNFL thinning, whereas 8 eyes (4.3%; 8 glaucoma patients) showed progressive reduction of RNFL retardance. Seven eyes (3.8%; 7 glaucoma patients) had progression that was detected by both instruments, all with progressive RNFL thinning detected before progressive reduction of RNFL retardance became evident, and the mean lag time was 13.4 months (range, 4.0-37.6 months). The agreement between RNFL thickness and RNFL retardance progression was fair (κ, 0.357). Progressive loss of RNFL thickness was observed most frequently at the inferotemporal 223° to 260°, whereas the inferotemporal 227° to 263° and superior 56° to 117° were observed most commonly for progressive loss of RNFL retardance. In the normal group, no eyes showed reduction in RNFL thickness or retardance. At a comparable level of specificity, progressive RNFL thinning was detected more often than progressive reduction of RNFL retardance. For eyes with progressive loss of RNFL thickness and RNFL retardance, the former preceded the latter.

β-Zone Parapapillary Atrophy and the Rate of Retinal Nerve Fiber Layer Thinning in Glaucoma

To evaluate whether β-zone parapapillary atrophy (PPA) is associated with the rate of retinal nerve fiber layer (RNFL) thickness change as assessed by trend-based analysis using time-domain optical coherence tomography (OCT). This retrospective cohort study included 202 glaucomatous eyes that were observed for ≥3 years with serial OCTs and stereo disc photographs. Subjects were divided into two groups according to the presence (n = 144) or absence of β-zone PPA (n = 58). The rates of progressive thinning in global, quadrant, and clock-hour OCT RNFL thicknesses were determined using linear regression and compared between groups. Logistic regression analysis was used to determine the factors associated with the rate of global RNFL thinning. The mean rate for global RNFL thinning over time was -1.03 ± 1.50 μm/year. Eyes with β-zone PPA showed a significantly faster rate of RNFL thinning than did eyes without β-zone PPA in the inferior quadrant and 7 o'clock sector (values of P < 0.0029). Multivariate analysis showed significant influence of the presence of β-zone PPA and the percentage increase in the PPA to disc area ratio during the follow-up on the rate of OCT RNFL thinning (odds ratio [OR], 3.314, P = 0.007; OR, 2.894, P = 0.003, respectively). Glaucomatous eyes with β-zone PPA are at increased risk for progressive RNFL thinning.

Trend-Based Analysis of Retinal Nerve Fiber Layer Thickness Measured by Optical Coherence Tomography in Eyes with Localized Nerve Fiber Layer Defects

To evaluate the rate of change in retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) in eyes with stable and progressive localized RNFL defects and to investigate, in a trend-based approach, the diagnostic capability of OCT in the detection of progressive RNFL thinning. The study included 153 glaucomatous eyes with localized RNFL defects. The patients were divided into nonprogressors (n = 77) and progressors (n = 76) on the basis of an evaluation of serial red-free photographs. The rates of progressive thinning in global, quadrant, and clock-hour OCT RNFL thicknesses were determined, by linear regression, and were compared between groups. Areas under receiver operating characteristic curves and sensitivities at fixed specificities were calculated for each parameter. The rate of progressive RNFL thinning was significantly faster in progressors than in nonprogressors globally; in the inferior quadrant; in the 10, 11, 6, and 7 o'clock sectors; and in the affected quadrant and clock-hour sector thicknesses (all P ≤ 0.001). The rate of RNFL thinning in affected clock-hour sectors had the highest ability to discriminate between stable and progressive RNFL thinning with a sensitivity of 62% (95% confidence interval, 50%-73%) at a specificity ≥80%. Agreement between OCT and red-free photography was strongest when the criterion of -3.6 μm/year with P < 0.1 was used for each clock hour. The rate of OCT RNFL thinning was significantly greater in patients with progressive localized RNFL defects than in those with stable localized defects. The data suggest that trend-based analysis of OCT RNFL thickness may be useful in glaucoma progression analysis and may complement other diagnostic tests.

Longitudinal study of vision and retinal nerve fiber layer thickness in multiple sclerosis

Cross-sectional studies of optical coherence tomography (OCT) show that retinal nerve fiber layer (RNFL) thickness is reduced in multiple sclerosis (MS) and correlates with visual function. We determined how longitudinal changes in RNFL thickness relate to visual loss. We also examined patterns of RNFL thinning over time in MS eyes with and without a prior history of acute optic neuritis (ON). Patients underwent OCT measurement of RNFL thickness at baseline and at 6-month intervals during a mean follow-up of 18 months at 3 centers. Low-contrast letter acuity (2.5%, 1.25% contrast) and visual acuity (VA) were assessed. Among 299 patients (593 eyes) with >or=6 months follow-up, eyes with visual loss showed greater RNFL thinning compared to eyes with stable vision (low-contrast acuity, 2.5%: p < 0.001; VA: p = 0.005). RNFL thinning increased over time, with average losses of 2.9microm at 2 to 3 years and 6.1microm at 3 to 4.5 years (p < 0.001 vs 0.5-1-year follow-up interval). These patterns were observed for eyes with or without prior history of ON. Proportions of eyes with RNFL loss greater than test-retest variability (>or=6.6microm) increased from 11% at 0 to 1 year to 44% at 3 to 4.5 years (p < 0.001). Progressive RNFL thinning occurs as a function of time in some patients with MS, even in the absence of ON, and is associated with clinically significant visual loss. These findings are consistent with subclinical axonal loss in the anterior visual pathway in MS, and support the use of OCT and low-contrast acuity as methods to evaluate the effectiveness of putative neuroprotection protocols.

Retinal Nerve Fiber Layer and Future Risk of Multiple Sclerosis

Optical coherence tomography (OCT)--measured retinal nerve fiber layer (RNFL) values may represent a surrogate biomarker for axonal integrity in multiple sclerosis (MS). The purpose of this study was to determine whether RNFL measurements obtained within two years of an optic neuritis (ON) event distinguish patients at increased risk of developing clinically-definite MS (CDMS). Fifty consecutively sampled patients who experienced a single ON event were followed prospectively for a mean period of 34 months with OCT testing. Values of RNFL in clinically-affected and non-affected eyes were compared between patients who developed CDMS and those that did not develop MS after ON. Twenty-one patients (42%) developed CDMS during the course of the study, with a mean conversion time of 27 months. Mean RNFL values were thinner in the clinically-affected eyes of non-MS patients than CDMS eyes after one year (p = 0.0462) due to more severe ON events in the former. By year two, CDMS patients manifested more recurrent ON events and RNFL thinning than non-MS patients. Temporal RNFL values were thinner in the non-affected eyes of CDMS patients with a trend towards significance (p = 0.1302). Our results indicate that RNFL thickness does not reliably distinguish patients at higher risk of converting to CDMS after ON. The severity of ON has a greater effect on RNFL thickness than risk of CDMS at one year. The CDMS patients demonstrate progressive RNFL thinning likely due to recurrent sub-clinical ON events, which may help differentiate them from non-MS patients over time.