Guihua Xu

Retinal Nerve Fiber Layer Imaging with Spectral-domain Optical Coherence Tomography: Patterns of Retinal Nerve Fiber Layer Progression

OBJECTIVE To examine the use of the retinal nerve fiber layer (RNFL) thickness map generated by a spectral-domain optical coherence tomography (OCT) to detect RNFL progression and identify the pattern of progressive changes of RNFL defects in glaucoma. DESIGN Prospective, longitudinal study. PARTICIPANTS One hundred eighty-six eyes of 103 glaucoma patients. METHODS Patients were followed at 4-month intervals for ≥ 36 months for RNFL imaging and visual field examination. Both eyes were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA) and had visual field testing at the same visits. We defined RNFL progression by Guided Progression Analysis (Carl Zeiss Meditec) of serial RNFL thickness maps. The pattern of RNFL progression was evaluated by comparing the baseline RNFL thickness deviation map and the RNFL thickness change map. Visual field progression was defined by trend analysis of visual field index and event analysis based on the Early Manifest Glaucoma Trial criteria. MAIN OUTCOME MEASURES The presence and the pattern of RNFL progression. RESULTS A total of 2135 OCT images were reviewed. Twenty-eight eyes (15.1%) from 24 patients (23.3%) had RNFL progression detected by RNFL thickness map analysis. Three RNFL progression patterns were observed: (1) widening of RNFL defects (24 eyes, 85.7%), (2) deepening of RNFL defects (2 eyes, 7.1%, both had concomitant widening of RNFL defects), and (3) development of new RNFL defects (5 eyes, 17.9%). The inferotemporal meridian (324°-336°) 2.0 mm away from the optic disc center was the most frequent location where RNFL progression was detected. Thirteen eyes (46.4%) had concomitant visual field progression; 61.5% (n = 8) of these had RNFL progression that preceded or occurred concurrently with visual field progression. Forty-two eyes from 37 patients (22.6%) had visual field progression by trend and/or event analyses without progression in the RNFL thickness map. CONCLUSIONS Analysis of serial RNFL thickness maps generated by the spectral-domain OCT facilitates the detection of RNFL progression in glaucoma.

Imaging the Iris with Swept-Source Optical Coherence Tomography: Relationship between Iris Volume and Primary Angle Closure

OBJECTIVE To measure iris volume and anterior segment parameters using a swept-source anterior segment optical coherence tomography (OCT) and investigate factors associated with iris volume and iris volume change after pupil dilation in eyes with open angles and angle closure. DESIGN Cross-sectional study. PARTICIPANTS A total of 86 eyes, including 31 eyes from 21 patients with primary angle closure (PAC) or PAC suspect, 31 eyes from 20 patients with primary open-angle glaucoma (POAG), and 24 eyes from 15 normal subjects, were included. METHODS The anterior segment parameters and iris were imaged and measured by the Casia SS-1000 OCT (Tomey, Nagoya, Japan) in room light, dark, and after pharmacologic dilation. Linear mixed models were used to examine the association between iris volume and change in iris volume after dilation and each of the following: age, sex, anterior chamber volume (ACV), axial length, pupil diameter, and angle width. MAIN OUTCOME MEASURES Iris volume. RESULTS The mean iris volume significantly decreased from light to dark and after pharmacologic dilation in angle closure (40.0 ± 5.2, 38.8 ± 5.4, and 32.5 ± 4.5 mm(3), respectively), POAG (40.2 ± 5.3, 39.4 ± 5.4, and 33.6 ± 4.2 mm(3), respectively), and normal eyes (40.1 ± 4.2, 39.1 ± 3.9, and 33.0 ± 4.4 mm(3), respectively). From room light to dark, the iris volume of 16.7% normal, 19.4% POAG, and 19.4% angle closure eyes increased iris volume (P = 0.960). After pharmacologic dilation, iris volume decreased in all eyes. Iris volume was negatively associated with ACV and positively associated with axial length (P<0.001). The change in iris volume per millimeter change in pupil diameter was 2.11, 2.01, and 1.80 mm(3)/mm in the angle closure, POAG, and normal groups, respectively (P≥0.414). A smaller ACV (P = 0.049) and older age (P = 0.036) were associated with a smaller change in iris volume per millimeter change in pupil diameter. A larger iris volume, smaller ACV, and greater pupil diameter were significant determinants of a smaller angle width (all P≤0.003). CONCLUSIONS The mean iris volume decreased after pupil dilation in open-angle and angle closure eyes, and the degree of reduction was less in eyes with a smaller ACV. Both iris volume and ACV were important determinants of the anterior chamber angle.

Optic Nerve Head Deformation in Glaucoma: A Prospective Analysis of Optic Nerve Head Surface and Lamina Cribrosa Surface Displacement

PURPOSE To evaluate long-term, longitudinal displacement of the optic nerve head (ONH) and anterior lamina cribrosa surfaces in glaucoma patients imaged with spectral-domain optical coherence tomography (SD OCT). DESIGN Prospective study. PARTICIPANTS A total of 173 eyes of 108 subjects (88 with glaucoma and 20 normal subjects) followed for a mean of 5.3 years. METHODS The optic disc was imaged with SD OCT at approximately 4-month intervals, and the ONH surface depth (ONHSD), anterior lamina cribrosa surface depth (ALCSD), and prelaminar tissue thickness (PTT) were measured. The reproducibility coefficients of ONHSD, ALCSD, and PTT were calculated from 2 baseline measurements of the glaucoma group. Change in ONHSD/ALCSD/PTT was confirmed when the differences between the first baseline and the latest 2 consecutive follow-up visits were greater than the corresponding reproducibility coefficient. Factors associated with ONHSD and ALCSD changes were identified with linear mixed modeling. MAIN OUTCOME MEASURES Proportion of eyes with ONHSD/ALCSD change. RESULTS Within the glaucoma group, 23.9% (33 eyes) had confirmed ONHSD change (15.2% with posterior and 8.7% with anterior displacement) and 24.6% (34 eyes) had confirmed ALCSD change (12.3% with posterior and 12.3% with anterior displacement). Some 9.4% (13 eyes) showed a decrease in PTT, and 2.2% (3 eyes) showed an increase in PTT. The specificity for detection of ONHSD/ALCSD/PTT change was 91.4% (95% confidence interval [CI], 77.6-97.0), 82.9% (95% CI, 67.3-91.9), and 94.3% (95% CI, 81.4-98.4), respectively. There were no significant differences in the proportion of eyes with visual field progression or history of filtration surgery between the groups with anterior and posterior displacement of ONH/anterior laminar surfaces (P ≥ 0.678). For each millimeter of mercury increase in the average intraocular pressure (IOP) during follow-up, the ONH and anterior laminar surfaces displaced posteriorly by 1.6 μm and 2.0 μm, respectively. An older age was associated with a decrease in magnitude of posterior displacement of the ONH and anterior laminar surfaces (P ≤ 0.009). CONCLUSIONS The ONH and anterior laminar surfaces displaced not only posteriorly but also anteriorly (with reference to Bruchs membrane opening) in a significant portion of glaucoma patients. The magnitude of change was related to age and the averaged IOP during follow-up.

Optic nerve head deformation in glaucoma: The temporal relationship between optic nerve head surface depression and retinal nerve fiber layer thinning

OBJECTIVE To investigate the temporal relationship between optic nerve head (ONH) surface depression and retinal nerve fiber layer (RNFL) thinning measured by confocal scanning laser ophthalmoscopy (CSLO) and spectral-domain optical coherence tomography (SD-OCT), respectively, during the course of glaucoma progression. DESIGN Prospective, longitudinal study. PARTICIPANTS A total of 146 eyes of 90 patients with glaucoma and 70 normal eyes of 35 healthy individuals followed for an average of 5.4 years (range, 48.0-76.6 months). METHODS Eyes were imaged by CSLO (Heidelberg Retinal Tomograph [HRT]; Heidelberg Engineering, GmbH, Dossenheim, Germany) and SD-OCT (Cirrus HD-OCT; Carl Zeiss Meditec AG, Dublin, CA) at approximately 4-month intervals for measurement of ONH surface topography and RNFL thickness, respectively. Significant ONH surface depression and RNFL thinning were defined with reference to Topographic Change Analysis (TCA) with HRT and Guided Progression Analysis (GPA) with Cirrus HD-OCT, respectively. The survival probabilities were compared with a Cox proportional hazards model. MAIN OUTCOME MEASURES Number of eyes with progressive ONH and RNFL changes and the sequence of changes. RESULTS A total of 3238 OCT and 3238 CSLO images obtained in the same follow-up visits were analyzed. At a specificity of 94.3% (4 eyes showed ONH surface depression and 4 eyes showed RNFL thinning in the normal group), 57 eyes (39.0%) had ONH surface depression, 46 eyes (31.5%) had RNFL thinning, and 23 eyes (15.8%) had evidence of both in the glaucoma group. Among these 23 eyes, 19 (82.6%) had ONH surface depression detected before RNFL thinning, with a median lag time of 15.8 months (range, 4.0-40.8 months). Although only 7.0% of eyes (4/57) had RNFL thinning at the onset of ONH surface depression, 45.7% (21/46) had ONH surface depression at the onset of RNFL thinning. The survival probability of eyes with ONH surface depression was significantly worse than eyes with RNFL thinning (P = 0.002). CONCLUSIONS With reference to the HRT TCA and OCT GPA, ONH surface depression occurred before RNFL thinning in a significant proportion of patients with glaucoma. A time window for therapeutic intervention may exist on detection of ONH surface depression before there is observable RNFL thinning in glaucoma.

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

OBJECTIVE 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. DESIGN Prospective, longitudinal study. PARTICIPANTS One hundred eighty-four eyes of 116 glaucoma patients and 43 normal eyes of 23 healthy individuals. METHODS 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. MAIN OUTCOME MEASURES Number of eyes with progressive RNFL changes over time. RESULTS 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. CONCLUSIONS 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.

Influence of ocular pulse amplitude on ocular response analyzer measurements.

PurposeTo evaluate if the ocular pulse amplitude (OPA) (the difference between systolic and diastolic intraocular pressure) is associated with the measurement variability of IOPg [Goldmann-correlated intraocular pressure (IOP)], IOPcc (corneal compensated IOP), corneal hysteresis (CH), and corneal resistance factor (CRF) obtained from the ocular response analyzer (ORA). MethodsSixty normal participants and 60 glaucoma patients were included. In 1 randomly selected eye in each participant, 4 repeated measurements were obtained with the ORA (Reichert Inc, Depew, NY) followed by OPA measurement by dynamic contour tonometry (Pascal; Swiss Microtechnology AG, Port, Switzerland). The repeatability of IOPg (a mathematically derived value with strong correlation with Goldmann applanation pressure measurement), IOPcc (a mathematically derived measurement less affected by corneal biomechanical properties), CH, and CRF were calculated. The associations between age, refraction, keratometry, central corneal thickness, axial length, OPA, and ORA measurements variability were evaluated with univariate and multivariate regression analyses. ResultsThe repeatability of IOPg, IOPcc, CRF, and CH were 4.08 (95% confidence interval: 3.06-5.09) mm Hg, 4.72 (3.54-5.89) mm Hg, 2.14 (1.61-2.68) mm Hg, 2.35 (1.77-2.94) mm Hg, respectively, for the normal group; and 4.18 (3.75-4.61) mm Hg, 5.56 (4.99-6.14) mm Hg, 2.17 (1.95-2.40) mm Hg, 2.78 (2.50-3.07) mm Hg, respectively, for the glaucoma group. Within-subject variances of IOPg and IOPcc, but not CRF and CH, were positively correlated with OPA. No association was found between age, refraction, keratometry, central corneal thickness, axial length, and the measurement variability of ORA. ConclusionsThe measurement reliability of ORA was only moderate. Eyes with large OPA were associated with high IOP measurement variability. Taking average of multiple repeated measurements is important for reliable measurement of ORA.

Electrical brain stimulation induces dendritic stripping but improves survival of silent neurons after optic nerve damage

Repetitive transorbital alternating current stimulation (rtACS) improves vision in patients with chronic visual impairments and an acute treatment increased survival of retinal neurons after optic nerve crush (ONC) in rodent models of visual system injury. However, despite this protection no functional recovery could be detected in rats, which was interpreted as evidence of “silent survivor” cells. We now analysed the mechanisms underlying this “silent survival” effect. Using in vivo microscopy of the retina we investigated the survival and morphology of fluorescent neurons before and after ONC in animals receiving rtACS or sham treatment. One week after the crush, more neurons survived in the rtACS-treated group compared to sham-treated controls. In vivo imaging further revealed that in the initial post-ONC period, rtACS induced dendritic pruning in surviving neurons. In contrast, dendrites in untreated retinae degenerated slowly after the axonal trauma and neurons died. The complete loss of visual evoked potentials supports the hypothesis that cell signalling is abolished in the surviving neurons. Despite this evidence of “silencing”, intracellular free calcium imaging showed that the cells were still viable. We propose that early after trauma, complete dendritic stripping following rtACS protects neurons from excitotoxic cell death by silencing them.