Marco Yu

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.

Impact of Age-related Change of Retinal Nerve Fiber Layer and Macular Thicknesses on Evaluation of Glaucoma Progression

OBJECTIVE To investigate the impact of age-related change of macular and circumpapillary retinal nerve fiber layer (RNFL) measurements on evaluation of glaucoma progression. DESIGN Prospective, longitudinal study. PARTICIPANTS A total of 150 eyes of 90 patients with glaucoma and 72 eyes of 40 normal individuals. METHODS Both eyes were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA; optic nerve head and macular scans were taken every 4 months for a mean of 45.8 months (range, 35.4-60.6 months). The mean age-related rates of change of macular (including the ganglion cell and inner plexiform layer [GCIPL], inner retina [IR], outer retina [OR], and total macular thicknesses) and circumpapillary RNFL measurements were estimated with linear mixed models in the normal group. Macular and RNFL progression were then evaluated in individual eyes in the glaucoma group, with trend analysis before and after accounting for age-related change using the lower 95% confidence intervals (CIs) of the mean age-related rates of change as cutoffs. The survival probability was evaluated with the Kaplan-Meier estimator, and the agreement of progression detection among the structural parameters was calculated with Kappa statistics. MAIN OUTCOME MEASURES Detection of glaucoma progression and survival probability of macular and RNFL parameters. RESULTS Before accounting for age-related change, 50.0% (75 eyes) showed progression by the GCIPL thickness, 50.0% (75 eyes) showed progression by the IR thickness, 30.0% (45 eyes) showed progression by the total macular thickness, 27.3% (41 eyes) showed progression by the circumpapillary RNFL thickness, and 10.0% (15 eyes) showed progression by the OR thickness. The survival probability of GCIPL and IR thicknesses were significantly worse compared with circumpapillary RNFL thickness (P ≤ 0.001). After accounting for age-related change, the proportions decreased to 14.7%, 20.0%, 16.0%, 26.7%, and 1.3%, respectively, with the circumpapillary RNFL thickness demonstrating the worst survival probability. The agreement of progression detection between RNFL and macular measurements was poor with (kappa range, -0.055 to 0.185) or without (kappa range, -0.046 to 0.173) taking age-related change into consideration. CONCLUSIONS Age-related change of macular and circumpapillary RNFL measurements can be detected in normal eyes and can affect the analysis of glaucoma progression. The impact is more substantial in analyzing macular progression than circumpapillary RNFL progression.

Anterior chamber angle imaging with swept-source optical coherence tomography: an investigation on variability of angle measurement.

PURPOSE To evaluate the reproducibility of anterior chamber angle measurements obtained by swept-source optical coherence tomography (OCT) and to identify factors associated with its measurement variability. METHODS One eye from each of 30 healthy subjects was randomly selected for anterior segment OCT imaging (Casia SS-1000 OCT; Tomey, Nagoya, Japan) in three separate visits within a week. The angle opening distance (AOD), the trabecular iris space area (TISA), and the trabecular-iris angle (TIA) at the superior (90°), nasal (0°), inferior (270°), and temporal (180°) angles were measured. The intraobserver and interobserver reproducibility coefficient (RC) and intraclass correlation coefficient (ICC) were calculated. Generalized linear latent and mixed modeling was used to examine the association between the variance of angle measurements and each of the following: angle width, pupil diameter, pupil diameter variance, iris thickness, iris thickness variance, axial length, anterior chamber depth, scan location, scleral spur visibility, and age. RESULTS The intervisit, intraobserver RCs ranged between 0.140 mm and 0.252 mm for AOD, 0.050 mm(2) and 0.090 mm(2) for TISA, and 7.7° and 9.5° for TIA, and the interobserver RCs were between 0.103 mm and 0.187 mm, 0.049 mm(2) and 0.101 mm(2), and 8.5° and 13.7°, respectively. The ICCs were all ≥0.83. Increased iris thickness, increased iris thickness variance, angle measured at the superior and inferior quadrants, increased angle width, and long axial length were associated with increased variance of angle measurements. CONCLUSIONS Although the swept-source OCT had high reproducibility for angle measurement, differences in iris thickness, angle width, measurement location, and axial length may influence its variability.

Retinal nerve fiber layer imaging with spectral-domain optical coherence tomography: interpreting the RNFL maps in healthy myopic eyes.

PURPOSE To investigate the association between the distribution profile of the retinal nerve fiber layer (RNFL) bundles and myopia and its impact on interpretation of the RNFL map imaged by a spectral-domain optical coherence tomography (SD-OCT). METHODS the RNFL of 189 myopic eyes from 103 normal healthy myopic participants was imaged by an SD-OCT. The angle between the long axes of the superotemporal and inferotemporal RNFL bundles determined in the RNFL thickness map (the RNFL distribution angle) and the abnormal area in the RNFL thickness deviation map were measured. The associations between the RNFL distribution angle and the axial length/spherical error, and between the area of abnormal RNFL measurement and each of the following: axial length, spherical error, RNFL distribution angle, average RNFL thickness, optic disc area, and signal strength were analyzed with linear mixed models. RESULTS The RNFL distribution angle decreased with the axial length (P < 0.011). In the univariate analysis, the area of abnormal RNFL measurement was positively associated with the axial length (P = 0.001); and negatively associated with the RNFL distribution angle (P < 0.001), average RNFL thickness (P < 0.001), optic disc area (P ≤ 0.001), and signal strength (P = 0.026). In the multivariate analysis, the area of abnormal RNFL measurement was negatively associated with the RNFL distribution angle independent of other covariates. CONCLUSIONS The superotemporal and inferotemporal RNFL bundles converged temporally with increasing myopia, which was associated with an increase in area of abnormal RNFL measurement. The interpretation of the RNFL thickness map in myopic eyes requires careful consideration of the distribution pattern of the RNFL bundles.

One-year outcomes of conventional and accelerated collagen crosslinking in progressive keratoconus

We compared one-year outcomes of conventional (3 mW/cm2, 365-nm ultraviolet-A light, 30 minutes) and accelerated (18 mW/cm2, 365-nm ultraviolet-A light, 5 minutes) collagen crosslinking (CXL) in patients with progressive keratoconus. Main outcome measures were change in keratometry, uncorrected visual acuity (UCVA), and best-corrected visual acuity (BCVA). Nineteen patients in each group completed 1-year follow-up. Preoperatively, there were no inter-group differences for age, keratometry, corneal thickness, and spherical equivalent (p > 0.127). One year postoperatively, maximum and minimum keratometry were flattened by 1.6 diopters (p < 0.023) and 2 diopters (p < 0.047) respectively after conventional CXL, and, 0.47 diopters (p = 0.471) and 0.19 diopters (p = 0.120) respectively after accelerated CXL. Association analysis showed significant negative association between baseline maximum keratometry and change in maximum keratometry after accelerated CXL (p = 0.002) but not after conventional CXL (p = 0.110). Corneal thickness was reduced significantly in both groups (p = 0.017). An improvement in UCVA (p < 0.001) and BCVA (p < 0.022) was noted in both groups along with a reduction in spherical equivalent postoperatively (p < 0.026). There were no inter-group differences for any of the parameters postoperatively (p > 0.184). Although no statistically significant differences were observed between both treatment modalities, a more effective topographic flattening was observed with conventional CXL as compared to accelerated CXL in this study.

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.

Tracking Dendritic Shrinkage of Retinal Ganglion Cells after Acute Elevation of Intraocular Pressure

PURPOSE To investigate dendritic changes of retinal ganglion cells (RGCs) and the rate of dendritic shrinkage after retinal ischemia induced by acute elevation of intraocular pressure (IOP). METHODS After elevating the IOP to 110 mm Hg for 30, 60, 90, and 120 minutes, a confocal scanning laser ophthalmoscope (CSLO) was used to serially image the retinas of the Thy-1 YFP transgenic mice in vivo for 1 to 3 months. Dendritic and axonal arborizations of 52 RGCs were visualized and followed longitudinally. Dendritic field, dendritic branching complexity (modified Sholl analysis), axonal diameter, and cell body area were measured. A total of 426 longitudinal measurements of dendritic field and dendritic complexity were analyzed for estimation of rate of change with linear mixed modeling. RESULTS There were no morphologic changes of RGCs after 30 (n = 12) or 60 (n = 12) minutes of ischemia. After 90 minutes of ischemia (n = 19), 78.9% of RGCs showed progressive loss of dendrites, axon, and cell body, 5.3% had only mild reduction of branching complexity and shrinkage of dendritic field whereas 15.8% showed no morphologic changes. All RGCs lost dendritic and axonal arborizations after 120 minutes of ischemia (n = 9). The rates of reduction of dendritic field were 11.7% per day (95% confidence interval, 5.0%-18.4% per day) after 90 minutes, and 15.1% per day (10.3%-19.9% per day) after 120 minutes of ischemia. CONCLUSIONS RGCs demonstrated dendritic shrinkage after 90 to 120 minutes, but not after 30 to 60 minutes of ischemia. In vivo imaging of dendritic changes could provide a sensitive approach to measure the rate of dendritic shrinkage after acute IOP elevation.

Corneal thickness and elevation measurements using swept-source optical coherence tomography and slit scanning topography in normal and keratoconic eyes.

To compare corneal thickness and corneal elevation using swept source optical coherence tomography and slit scanning topography.

Optic Disc Imaging with Spectral-Domain Optical Coherence Tomography: Variability and Agreement Study with Heidelberg Retinal Tomograph

OBJECTIVE To evaluate the agreement of optic disc measurements obtained with the Cirrus high-density optical coherence tomography (HD-OCT) and the Heidelberg retina tomograph (HRT) and compare the intervisit, test-retest variability between the instruments. DESIGN Prospective, cross-sectional study. PARTICIPANTS Two hundred seven subjects (109 glaucoma and 98 normal subjects). METHODS One eye from each individual was selected randomly for optic disc imaging by the Cirrus HD-OCT and the HRT. Areas of the optic disc and the cup, cup volume, vertical cup-to-disc ratio and cup-to-disc area ratio were compared between the instruments. The OCT measurements were corrected for ocular magnification using the Littmans formula. The measurement agreement was evaluated with the Bland-Altman plots. The intervisit test-retest variability was examined in 17 randomly selected glaucoma patients who underwent optic disc imaging weekly for 8 consecutive weeks. The intraclass correlation coefficients (ICC) and the reproducibility coefficients of the optic disc parameters were computed. MAIN OUTCOME MEASURES Measurement agreement, reproducibility coefficients, and ICCs of optic disc parameters. RESULTS The OCT measured smaller optic disc and rim areas and greater cup volume, vertical cup-to-disc ratio and cup-to-disc area ratio than the HRT did (all with P<0.001). There were proportional biases in the Bland-Altman plots between OCT and HRT optic disc measurements except for rim area and cup-to-disc area ratio. The 95% limits of agreement of rim area ranged between -0.28 and 0.88 mm(2) before, and between -0.22 and 0.92 mm(2) after correction for ocular magnification. Both OCT and HRT showed high test-retest reproducibility with ICCs ≥ 0.921. Although the reproducibility coefficient of OCT rim area (0.093 mm(2); 95% confidence interval [CI], 0.081-0.105 mm(2)) was significantly smaller than that of the HRT (0.186 mm(2); 95% CI, 0.163-0.210 mm(2); P = .018), there were no differences in the ICCs between the instruments. CONCLUSIONS Optic disc assessment by spectral-domain OCT and confocal scanning laser ophthalmoscopy demonstrates poor agreement but similarly low test-retest variability. The source of their disagreement and its effects on the detection of progression require further study.

Comparison of Retinal Nerve Fiber Layer Imaging by Spectral Domain Optical Coherence Tomography and Scanning Laser Ophthalmoscopy

OBJECTIVE To compare the area and the angular width of localized retinal nerve fiber layer (RNFL) defects imaged by confocal scanning laser ophthalmoscopy (CSLO) and optical coherence tomography (OCT) and to evaluate their agreement. DESIGN Cross-sectional study. PARTICIPANTS Fifty-one eyes of 41 glaucoma patients. METHODS Sixty-one distinctive, localized RNFL defects (17 superior and 44 inferior RNFL defects) detected in RNFL photographs imaged by a CSLO were identified. These patients underwent RNFL imaging with a spectral-domain OCT. The RNFL thickness deviation maps (50×50 pixels) generated by the OCT revealed the locations of abnormal RNFL thicknesses with abnormal pixels denoted in red (RNFL thickness less than the lower 99% normal distribution) or yellow (RNFL thickness less than the lower 95% normal distribution). The RNFL thickness deviation maps were aligned and overlaid with the corresponding CSLO RNFL photographs. The area and the angular width of RNFL defects from the corresponding retinal regions in the CSLO RNFL photographs and the OCT RNFL thickness maps were measured and compared. Their agreement was analyzed with the Bland-Altman plot. MAIN OUTCOME MEASURES The area and the angular width of RNFL defects and the agreement of RNFL defects measurements between OCT images and CSLO RNFL photographs. RESULTS The area and the angular width of RNFL defects measured with the CSLO RNFL photographs were 1.11 ± 0.57 mm² and 23.80 ± 10.38°, respectively, which were significantly smaller than those measured by the OCT RNFL thickness deviation map when abnormal RNFL thickness was defined as less than the lower 95% centile ranges (2.27 ± 0.92 mm² and 74.16 ± 28.74°, respectively; both P < 0.001). When abnormal RNFL thickness was defined as less than the lower 99% centile ranges, a significant difference in angular width (42.11 ± 22.19°; P<0.001), but not in area (1.19 ± 0.68 mm²; P = 0.444) was found between the 2 imaging methods. Bland-Altman plots revealed that a larger RNFL defect was associated with a greater difference in angular width between OCT and CSLO RNFL photography measurements. CONCLUSIONS The agreement of RNFL defect measurements between CSLO RNFL photography and OCT was poor. The OCT RNFL thickness deviation map could reveal additional RNFL abnormalities not detectable by CSLO RNFL photography. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.