Gilda Lai

Retinal Nerve Fiber Layer Imaging with Spectral-Domain Optical Coherence Tomography Analysis of the Retinal Nerve Fiber Layer Map for Glaucoma Detection

OBJECTIVE To evaluate the diagnostic performance of the retinal nerve fiber layer (RNFL) thickness deviation map imaged by a spectral-domain optical coherence tomography (OCT; Cirrus HD-OCT, Carl Zeiss Meditec Inc, Dublin, CA) and compare its sensitivity and specificity for glaucoma detection with circumpapillary RNFL measurement derived from the standard 3.46 mm diameter circle scan. DESIGN Prospective, cross-sectional study. PARTICIPANTS We included 102 normal subjects and 121 glaucoma patients. METHODS One eye from each individual was imaged with Cirrus HD-OCT and Stratus OCT (Carl Zeiss Meditec Inc.). Glaucoma was defined based on the presence of visual field defects with the Humphrey visual field analyzer (Carl Zeiss Meditec Inc.). A scoring system (0-5) was developed to analyze the RNFL thickness deviation map taking the defect size, shape, depth, location, and distance from the disc margin into consideration. Each of these features was scored independently by a masked observer with a highest total score of 5 (glaucomatous RNFL defect) and a lowest score of 0 (no RNFL defect). Sensitivity and specificity were computed with a score of > or =3, > or =4, or =5. The diagnostic performance of circumpapillary RNFL measurement was analyzed with clock-hour and average RNFL thickness categorical classification. MAIN OUTCOME MEASURES Diagnostic sensitivity and specificity. RESULTS The sensitivities of the RNFL thickness deviation map ranged between 95.0% and 97.5%. There were significant differences in specificity between a map score of 5, a map score of > or =4 (87.3%), and a map score > or =3 (72.5%; P< or =0.014). A map score of 5 attained a significantly higher sensitivity (95.0%) compared with clock-hour or average RNFL thickness categorical classification by Stratus OCT or Cirrus HD-OCT (46.3%-88.4%; P< or =0.033) at a comparable level of specificity (95.1%), except when glaucoma was detected as having > or =1 clock-hour at the < or =5% level by Cirrus HD-OCT in which an equally high sensitivity (93.4%) was found but at the expense of a significantly lower specificity (83.3%; P<0.001). CONCLUSIONS Analysis of the RNFL thickness deviation map provides additional spatial and morphologic information of RNFL damage and significantly improves the diagnostic sensitivity for glaucoma detection compared with conventional circumpapillary RNFL measurement.

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.

Retinal Nerve Fiber Layer Imaging with Spectral-Domain Optical Coherence Tomography: Pattern of RNFL Defects in Glaucoma

OBJECTIVE To characterize the distribution pattern, angular width, and area of retinal nerve fiber layer (RNFL) defects in glaucoma using spectral-domain optical coherence tomography (OCT). DESIGN Prospective, cross-sectional study. PARTICIPANTS We included 113 normal subjects and 116 glaucoma patients. METHODS One eye from each individual was randomly selected for Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, CA) RNFL imaging of the 6 × 6-mm² parapapillary region. The RNFL defects were identified in the RNFL thickness deviation map as superpixels coded in red. The angular location and the angular width of RNFL defects were measured. The proportion of area with RNFL measurements within the normal ranges in the RNFL thickness deviation map was expressed as the RNFL area index (RAI): 1 - [area of superpixels coded in red/(6 × 6 - optic disc and parapapillary atrophic area)]. The diagnostic performance between RAI and average RNFL thickness was compared with the area under the receiver operating characteristic curve after adjusting refraction, signal strength, optic disc, and parapapillary atrophic areas. MAIN OUTCOME MEASURES Frequency distribution profiles and distribution patterns of RNFL defects, diagnostic sensitivity and specificity of RAI, and average RNFL thickness. RESULTS The RNFL defects in glaucoma were most frequently found at the inferotemporal meridian at 284° (80.4%), followed by the superotemporal meridians at 73° (54.2%). The respective proportions of localized (angular width ≤ 30°) and diffuse (angular width > 30°) RNFL defects were 11.4% and 70.5% in mild glaucoma (MD ≥ 6 dB), and 4.2% and 94.5% in moderate to advanced glaucoma (MD < -6 dB). The RAI was 90.2 ± 6.4% and 83.6 ± 7.4% in the mild and moderate to advanced glaucoma groups, respectively. At a specificity of 90.0%, the respective diagnostic sensitivity of RAI and average RNFL thickness was 95.7% (95% confidence interval, 92.2-99.1%) and 94.0% (90.1-99.1%). CONCLUSIONS Analysis of the pattern of RNFL defects with spectral domain OCT imaging offers important insights in understanding the characteristics of RNFL damage. As RNFL defects expand in size as the disease progresses, measurement of the angular width and area of RNFL defects can provide an additional dimension for evaluation of glaucoma.

Evaluation of Retinal Nerve Fiber Layer Progression in Glaucoma: A Prospective Analysis with Neuroretinal Rim and Visual Field Progression

OBJECTIVE To evaluate the performance of progression detection and the rate of change of retinal nerve fiber layer (RNFL), neuroretinal rim, and visual field measurements in glaucoma. DESIGN Prospective study. PARTICIPANTS One hundred eight eyes of 70 glaucoma patients. METHODS Patients were followed up every 4 months for at least 2.9 years (median, 3.2 years) for measurement of RNFL thickness with the Stratus optical coherence tomograph (OCT) (Carl Zeiss Meditec, Dublin, CA), neuroretinal rim area with the Heidelberg Retinal Tomograph (HRT 3; Heidelberg Engineering, GmbH, Dossenheim, Germany), and visual field with the Humphrey Field Analyzer II (Carl Zeiss Meditec). Linear regression analyses were performed between visual field index (VFI), RNFL, and neuroretinal rim measurements and age, with progression defined when a significant negative trend was detected. The agreement among structural and functional measurements was evaluated with κ statistics. The mean rate of change was estimated with linear mixed modeling. MAIN OUTCOME MEASURES The agreement on progression detection and the rate of change of RNFL, neuroretinal rim, and VFI measurements. RESULTS A total of 1105 OCT, 1062 HRT, and 1099 visual field measurements were analyzed. The agreement of progression detection among the 3 investigations was poor (κ≤0.09). Ten eyes (9.3%; 9 patients) showed progression by average RNFL thickness, 16 (14.8%; 14 patients) by global neuroretinal rim area, and 35 (32.4%; 31 patients) by VFI. Only 1 eye (0.9%) had progression detected by all 3 methods. There were large variations in the rate of change of VFI, average RNFL thickness, and global neuroretinal rim area, with a range between -0.63% and -4.97% per year, -2.32% and -10.12% per year, and -0.61% and -8.48% per year, respectively. The respective mean rate estimates were -1.15% per year (95% confidence interval [CI], -1.56% to -0.73%), -0.70% per year (95% CI, -1.19% to -0.21%), and -1.06% per year (95% CI, -1.56% to -0.55%). CONCLUSIONS The agreement of progression detection among RNFL, neuroretinal rim, and visual field measurements was poor, and the rate of RNFL, neuroretinal rim, and visual field progression varied considerably within and between subjects. Given this variability, interpretation of RNFL, neuroretinal rim, and VFI progression always should be evaluated on an individual basis. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

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.

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.

Comparison of Standard Automated Perimetry, Frequency-Doubling Technology Perimetry, and Short-Wavelength Automated Perimetry for Detection of Glaucoma

PURPOSE To compare the performance of standard automated perimetry (SAP), frequency-doubling technology (FDT) perimetry, and short-wavelength automated perimetry (SWAP) in detecting glaucoma. METHODS One hundred thirty-two eyes of 95 glaucoma patients and 37 normal subjects had retinal nerve fiber layer (RNFL) imaging and visual field testing by SAP, Matrix FDT perimetry, and Swedish interactive thresholding algorithm (SITA) SWAP at the same visit (all perimeters by Carl Zeiss Meditec, Inc., Dublin, CA). Visual field defects were confirmed with two or more consecutive examinations by the same types of perimetry. Glaucoma was defined with the reference to the RNFL thickness deviation map score (≥ 4, glaucomatous; ≤ 2, normal). The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of MD (mean deviation) and PSD (pattern standard deviation) of the perimetries were compared. RESULTS Taking all glaucoma patients into consideration, the sensitivity was highest for Matrix FDT perimetry (69%), followed by SAP (68%), and then SITA SWAP (59%). When the analysis included only patients with early glaucoma, the sensitivity decreased to 52%, 46%, and 34%, respectively, with a significant difference detected between Matrix FDT perimetry and SITA SWAP (P = 0.034). The specificity was ≥ 97% for all perimetries. The AUCs of MD and PSD followed a similar order, with Matrix FDT perimetry having the greatest AUC (0.89-0.94), followed by SAP (0.87-0.94), and then SITA SWAP (0.69-0.90). There were significant differences in sensitivities at 90% specificity between Matrix FDT perimetry and SITA SWAP (P ≤ 0.005 for MD; P ≤ 0.039 for PSD). CONCLUSIONS The performance for glaucoma detection was comparable between FDT perimetry and SAP. FDT perimetry had a higher sensitivity for detecting glaucoma than did SWAP at a comparable level of specificity.

Variability of Corneal Deformation Response in Normal and Keratoconic Eyes.

PurposeTo compare the corneal deformation response, central corneal thickness (CCT), and intraocular pressure (IOP) measurements and their test-retest variability obtained with an ultrahigh-speed Scheimpflug camera between normal and keratoconus eyes. MethodsThree consecutive measurements were obtained using Corvis ST. The following parameters were analyzed: A1 and A2 length (length of flattened cornea at first and second applanation), A1 and A2 velocity (deformation velocity until first and second applanation), corneal deformation amplitude (deformation amplitude of cornea at the highest concavity), peak distance (distance of two apices of cornea at time of highest concavity), and radius of corneal curvature at the time of maximum deformation. Repeatability coefficient and intraclass correlation coefficient were measured. Linear mix models were used to adjust for the effect of age, CCT, and IOP on corneal deformation response parameters. ResultsTwelve normal subjects and 12 keratoconus patients were included. Data from only one eye of each participant were randomly selected for analysis. Significant differences were found in corneal deformation amplitude (p < 0.001) and radius of corneal curvature (p < 0.001) between normal and keratoconus eyes after adjusting for age, CCT, and IOP. Although there was no significant difference of intraclass correlation coefficient between the groups, repeatability coefficient values of A1 and A2 length, A1 velocity, and peak distance were significantly smaller in normal eyes as compared with keratoconus eyes (p ⩽ 0.023). ConclusionsCorvis ST showed adequate repeatability for measurement of corneal deformation amplitude, CCT, and IOP in normal and keratoconus eyes. It may be used to understand ocular pathologies associated with altered biomechanical properties.

Frequency-Doubling Technology Perimetry for Detection of the Development of Visual Field Defects in Glaucoma Suspect Eyes: A Prospective Study

IMPORTANCE While standard automated perimetry (SAP) remains the reference standard for evaluation of visual field (VF) defects in glaucoma, this study demonstrates that frequency-doubling technology (FDT) perimetry is effective in monitoring visual field progression and may detect the onset of visual field defects earlier than SAP. OBJECTIVES To compare detection of the development of VF defects, rate of change of VF loss, and risk factors for progression between SAP and matrix FDT perimetry in glaucoma suspect and ocular hypertensive eyes. DESIGN, SETTING, AND PARTICIPANTS A total of 113 glaucoma suspect and ocular hypertensive eyes from 76 patients with normal SAP and FDT perimetry results at baseline were prospectively followed up for SAP and FDT perimetry testing at approximately 4-month intervals for 30 months or longer. Patients were consecutively enrolled and followed up from January 2, 2008, to February 28, 2012, at the Hong Kong Eye Hospital, Chinese University of Hong Kong. Visual field progression was defined by the development of VF defects confirmed by 3 or more consecutive examinations at a cluster of 3 or more (less conservative) or 4 or more (more conservative) locations. The rates of change of mean deviation and pattern standard deviation were evaluated with linear mixed models and the risk factors for VF progression were computed with Cox proportional hazard models. RESULTS During a median study period of 3.4 years, 8.0% of eyes developed VF defects detected by FDT perimetry, 6.2% by SAP, and 4.4% by both using the less-conservative criteria. The detection dropped to 6.2%, 4.4%, and 2.7%, respectively, when the more-conservative criteria were applied. The rate of change of pattern standard deviation was significantly faster for FDT perimetry than SAP (P < .001). Baseline average retinal nerve fiber layer thickness and the number of clock hours of abnormal retinal nerve fiber layer measurement were associated with increased risk for VF progression for both SAP and FDT perimetry. CONCLUSIONS AND RELEVANCE Frequency-doubling technology perimetry would be useful to monitor the onset of VF defects in glaucoma and may detect VF defects not evident in SAP.

Frequency Doubling Technology Perimetry for Detection of Visual Field Progression in Glaucoma: A Pointwise Linear Regression Analysis

PURPOSE We compared the detection of visual field progression and its rate of change between standard automated perimetry (SAP) and Matrix frequency doubling technology perimetry (FDTP) in glaucoma. METHODS We followed prospectively 217 eyes (179 glaucoma and 38 normal eyes) for SAP and FDTP testing at 4-month intervals for ≥36 months. Pointwise linear regression analysis was performed. A test location was considered progressing when the rate of change of visual sensitivity was ≤-1 dB/y for nonedge and ≤-2 dB/y for edge locations. Three criteria were used to define progression in an eye: ≥3 adjacent nonedge test locations (conservative), any three locations (moderate), and any two locations (liberal) progressed. The rate of change of visual sensitivity was calculated with linear mixed models. RESULTS Of the 217 eyes, 6.1% and 3.9% progressed with the conservative criteria, 14.5% and 5.6% of eyes progressed with the moderate criteria, and 20.1% and 11.7% of eyes progressed with the liberal criteria by FDTP and SAP, respectively. Taking all test locations into consideration (total, 54 × 179 locations), FDTP detected more progressing locations (176) than SAP (103, P < 0.001). The rate of change of visual field mean deviation (MD) was significantly faster for FDTP (all with P < 0.001). No eyes showed progression in the normal group using the conservative and the moderate criteria. CONCLUSIONS With a faster rate of change of visual sensitivity, FDTP detected more progressing eyes than SAP at a comparable level of specificity. Frequency doubling technology perimetry can provide a useful alternative to monitor glaucoma progression.