Crystalline lens nuclear age prediction as a new biomarker of nucleus degeneration.

BACKGROUND: The crystalline lens is a transparent structure of the eye to focus light on the retina. It becomes muddy, hard and dense with increasing age, which makes the crystalline lens gradually lose its function. We aim to develop a nuclear age predictor to reflect the degeneration of the crystalline lens nucleus. METHODS: First we trained and internally validated the nuclear age predictor with a deep-learning algorithm, using 12 904 anterior segment optical coherence tomography (AS-OCT) images from four diverse Asian and American cohorts: Zhongshan Ophthalmic Center with Machine0 (ZOM0), Tomey Corporation (TOMEY), University of California San Francisco and the Chinese University of Hong Kong. External testing was done on three independent datasets: Tokyo University (TU), ZOM1 and Shenzhen People's Hospital (SPH). We also demonstrate the possibility of detecting nuclear cataracts (NCs) from the nuclear age gap. FINDINGS: In the internal validation dataset, the nuclear age could be predicted with a mean absolute error (MAE) of 2.570 years (95% CI 1.886 to 2.863). Across the three external testing datasets, the algorithm achieved MAEs of 4.261 years (95% CI 3.391 to 5.094) in TU, 3.920 years (95% CI 3.332 to 4.637) in ZOM1-NonCata and 4.380 years (95% CI 3.730 to 5.061) in SPH-NonCata. The MAEs for NC eyes were 8.490 years (95% CI 7.219 to 9.766) in ZOM1-NC and 9.998 years (95% CI 5.673 to 14.642) in SPH-NC. The nuclear age gap outperformed both ophthalmologists in detecting NCs, with areas under the receiver operating characteristic curves of 0.853 years (95% CI 0.787 to 0.917) in ZOM1 and 0.909 years (95% CI 0.828 to 0.978) in SPH. INTERPRETATION: The nuclear age predictor shows good performance, validating the feasibility of using AS-OCT images as an effective screening tool for nucleus degeneration. Our work also demonstrates the potential use of the nuclear age gap to detect NCs.

Diagnostic assessment of glaucoma and non-glaucomatous optic neuropathies via optical texture analysis of the retinal nerve fibre layer.

The clinical diagnostic evaluation of optic neuropathies relies on the analysis of the thickness of the retinal nerve fibre layer (RNFL) by optical coherence tomography (OCT). However, false positives and false negatives in the detection of RNFL abnormalities are common. Here we show that an algorithm integrating measurements of RNFL thickness and reflectance from standard wide-field OCT scans can be used to uncover the trajectories and optical texture of individual axonal fibre bundles in the retina and to discern distinctive patterns of loss of axonal fibre bundles in glaucoma, compressive optic neuropathy, optic neuritis and non-arteritic anterior ischaemic optic neuropathy. Such optical texture analysis can detect focal RNFL defects in early optic neuropathy, as well as residual axonal fibre bundles in end-stage optic neuropathy that were indiscernible by conventional OCT analysis and by red-free RNFL photography. In a diagnostic-performance study, optical texture analysis of the RNFL outperformed conventional OCT in the detection of glaucoma, as defined by visual-field testing or red-free photography. Our findings show that optical texture analysis of the RNFL for the detection of optic neuropathies is highly sensitive and specific.

Nicotinamide riboside as a neuroprotective therapy for glaucoma: study protocol for a randomized, double-blind, placebo-control trial.

BACKGROUND: Whereas lowering the intraocular pressure (IOP) can slow optic nerve degeneration in glaucoma, many patients with glaucoma continue to develop progressive loss in vision despite a significant reduction in IOP. No treatment has been shown to be effective for neuroprotection in glaucoma. We set out to conduct a randomized controlled trial to investigate whether nicotinamide riboside (NR), a nicotinamide adenine dinucleotide precursor, is effective to slow optic nerve degeneration in patients with primary open-angle glaucoma (POAG). We hypothesize that patients treated with NR have a slower rate of progressive retinal nerve fiber layer (RNFL) thinning compared with those treated with placebo. METHODS: This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study including 125 patients with POAG. Patients will be randomized to receive 300 mg NR or placebo for 24 months. Clinical examination, optical coherence tomography imaging of the RNFL, and visual field (VF) test will be performed at the baseline, 1 month, 4 months, and then at 2-month intervals until 24 months. The primary outcome measure is the rate of RNFL thinning measured over 24 months. The secondary outcome measures include (1) time to VF progression, (2) time to progressive RNFL/ganglion cell inner plexiform layer (GCIPL) thinning, and (3) the rate of change of VF sensitivity over 24 months (to investigate neuroprotection) and 1 month (to investigate neuroenhancement). The rates of RNFL thinning and VF sensitivity decline between treatment groups will be compared with linear mixed modeling. Survival analysis will be performed to compare the differences in time from baseline to VF progression and time from baseline to progressive RNFL/GCIPL thinning between treatment groups using Cox proportional hazards models. DISCUSSION: Outcome measures in glaucoma neuroprotection trials have been centered on the detection of VF progression, which may take years to develop and confirm. In addition to addressing whether NR has a neuroprotective/neuroenhancement effect in glaucoma patients, this study will demonstrate the feasibility of studying neuroprotection in a relatively short trial period (24 months) by comparing the rates of progressive RNFL thinning, a more reproducible and objective outcome measure compared with VF endpoints, between treatment groups. TRIAL REGISTRATION: Chinese Clinical Trial Registry 1900021998.

Comparison of two novel swept-source optical coherence tomography devices to a partial coherence interferometry-based biometer.

To evaluate the repeatability and agreement of corneal and biometry measurements obtained with two swept-source optical coherence tomography (SSOCT) and a partial coherence interferometry-based device. This is a cross-sectional study. Forty-eight eyes of 48 patients had three consecutive measurements for ANTERION (Heidelberg Engineering, Germany), CASIAII (Tomey, Japan) and IOLMaster500 (Carl Zeiss Meditec, USA) on the same visit. Mean keratometry (Km), central corneal thickness (CCT), anterior chamber depth (ACD) and axial length (AL) were recorded. Corneal astigmatic measurements were converted into vector components-J0 and J45. Intra-device repeatability and agreements of measurements amongst the devices were evaluated using repeatability coefficients (RCs) and Bland-Altman plots, respectively. All devices demonstrated comparable repeatability for Km (p ≥ 0.138). ANTERION had the lowest RC for J0 amongst the devices (p ≤ 0.039). Systematic difference was found for the Km and J0 obtained with IOLMaster500 compared to either SSOCTs (p ≤ 0.010). The ACD and AL measured by IOLMaster500 showed a higher RC compared with either SSOCTs (p < 0.002). Systematic difference was found in CCT and ACD between the two SSOCTs (p < 0.001), and in AL between ANTERION and IOLMaster500 (p < 0.001), with a mean difference of 1.6 µm, 0.022 mm and 0.021 mm, respectively. Both SSOCTs demonstrated smaller test-retest variability for measuring ACD and AL compared with IOLMaster500. There were significant disagreement in keratometry and AL measurements between the SSOCTs and PCI-based device; their measurements should not be considered as interchangeable.

Efficacy and safety of selective laser trabeculoplasty and pattern scanning laser trabeculoplasty: a randomised clinical trial.

AIMS: To compare the intraocular pressure (IOP) lowering effect and safety profile between pattern scanning laser trabeculoplasty (PSLT) and selective laser trabeculoplasty (SLT) in patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) over a 12-month follow-up. METHODS: 132 patients with POAG or OHT were consecutively enrolled and randomised (1:1) to receive PSLT (n=65) or SLT (n=67) in a single centre. IOP was measured before and then on 1 day, 1 week, 1, 3, 6, 9 and 12 months after PSLT/SLT. The primary outcome measure was the proportion of patients with ≥20% IOP reduction at 12 months without IOP-lowering medications (complete success). RESULTS: The mean baseline IOP was 21.2±4.1 mm Hg for eyes randomised to PSLT and 21.3±4.7 mm Hg for eyes randomised to SLT (p=0.898). At 12 months, the IOP was 18.3±3.1 and 17.8±3.4 mm Hg, respectively (p=0.402). IOP measurements were comparable between the groups over 12 months (overall mean difference 0.4 mm Hg, 95% CI: -0.5 to 1.3 mm Hg). 15.4% of PSLT-treated and 25.4% of SLT-treated patients achieved treatment success (difference: 10.0%, 95% CI: -3.6 to 23.6) (p=0.155), respectively. A higher baseline IOP and a greater percentage of IOP reduction at day 1 were associated with a greater percentage of IOP reduction at 12 months (p<0.001). There were no significant differences in visual field mean deviation, average retinal nerve fibre layer thickness, corneal endothelial cell count and visual acuity between the treatment groups at the baseline and 12-month follow-up (p≥0.062). CONCLUSIONS: PSLT was not superior to SLT in terms of safety and IOP-lowering efficacy in patients with POAG or OHT. TRIAL REGISTRATION NUMBER: The clinical trial was registered in the Centre for Research and Biostatistics Clinical Trials Registry, the Chinese University of Hong Kong (Identifier CUHK_CCT00407). The full trial protocol can be accessed from the authors on request.

Anterior chamber angle imaging with swept-source optical coherence tomography: comparison between CASIAII and ANTERION.

This study compared the test-retest variabilities and measurement agreement of anterior chamber angle (ACA) dimensions measured by two anterior segment swept-source optical coherence tomography (SS-OCT)-the ANTERION (Heidelberg Engineering, Heidelberg, Germany) and CASIAII (Tomey, Nagoya, Japan). Thirty-eight subjects, 18 patients with primary angle closure and 20 healthy participants with open angles, were included. The mean age was 54.7 ± 15.8 years (range: 26-75 years). One eye of each subject was randomly selected for anterior segment imaging by ANTERION and CASIAII, using the same scan pattern (6 evenly spaced radial scans across the anterior segment for three times) in the same visit. The between- and within-instrument agreement and repeatability coefficients of angle open distance (AOD500), trabecular-iris space area (TISA500), lens vault (LV), scleral spur-scleral spur distance (SSD), anterior chamber depth (ACD), and pupil diameter (PD) were measured. The anterior and posterior boundaries of the cornea, iris, and lens were automatically segmented by the SS-OCT instruments; the scleral spur was manually located by a single masked observer. There were significant differences between ANTERION and CASIAII measurements; the SSD, PD, and ACD were smaller whereas AOD500 and TISA500 were greater in ANTERION compared with CASIAII (P < 0.001). Anterior segment measurements obtained from the two SS-OCT instruments showed strong associations (R2 ranged between 0.866 and 0.998) although the between-instrument agreement was poor; the spans of 95% limits of between-instrument agreement were ≥ 1.5-folds than the within-instrument agreement for either instrument. Whereas both SS-OCT instruments showed low test-retest measurement variabilities, the repeatability coefficients of AOD500, TISA500, ACD, and PD were slightly smaller for CASIAII than ANTERION (P ≤ 0.012).

Use of Virtual Reality Simulation to Identify Vision-Related Disability in Patients With Glaucoma.

Importance: Clinical assessment of vision-related disability is hampered by the lack of instruments to assess visual performance in real-world situations. Interactive virtual reality (VR) environments displayed in a binocular stereoscopic VR headset have been designed, presumably simulating day-to-day activities to evaluate vision-related disability. Objective: To investigate the application of VR to identify vision-related disability in patients with glaucoma. Design, Setting, and Participants: In a cross-sectional study, 98 patients with glaucoma and 50 healthy individuals were consecutively recruited from a university eye clinic; all participants were Chinese. The study was conducted between August 30, 2016, and July 31, 2017; data analysis was performed from December 1, 2017, to October 30, 2018. Exposures: Measurements of visual acuity, contrast sensitivity, visual field (VF), National Eye Institute 25-item Visual Function Questionnaire Rasch score, and VR disability scores determined from 5 VR simulations: supermarket shopping, stair and city navigations in daytime, and stair and city navigations in nighttime. Duration required to complete the simulation, number of items incorrectly identified, and number of collisions were measured to compute task-specific and overall VR disability scores. Vision-related disability was identified when the VR disability score was outside the normal age-adjusted 95% confidence region. Main Outcomes and Measures: Virtual reality disability score. Results: In the 98 patients with glaucoma, mean (SD) age was 49.8 (11.6) years and 60 were men (61.2%); in the 50 healthy individuals, mean (SD) age was 48.3 (14.8) years and 16 were men (32.0%). The patients with glaucoma had different degrees of VF loss (122 eyes [62.2%] had moderate or advanced VF defects). The time required to complete the activities by patients with glaucoma vs healthy individuals was longer by 15.2 seconds (95% CI, 5.5-24.9 seconds) or 34.1% (95% CI, 12.4%-55.7%) for the shopping simulation, 72.8 seconds (95% CI, 23.0-122.6 seconds) or 33.8% (95% CI, 10.7%-56.9%) for the nighttime stair navigation, and 38.1 seconds (95% CI, 10.9-65.2 seconds) or 30.8% (95% CI, 8.8%-52.8%) for the nighttime city navigation. The mean (SD) duration was not significantly different between the glaucoma and healthy groups in daytime stair (203.7 [93.7] vs 192.9 [89.1] seconds, P = .52) and city (118.7 [41.5] vs 117.0 [52.3] seconds, P = .85) navigation. For each decibel decrease in binocular VF sensitivity, the risk of collision increased by 15% in nighttime stair (hazard ratio [HR], 1.15; 95% CI, 1.08-1.22) and city (HR, 1.15; 95% CI, 1.08-1.23) navigations. Fifty-eight patients (59.1%) with glaucoma had vision-related disability in at least 1 simulated daily task; a higher proportion of patients had vision-related disability in nighttime city (27 of 88 [30.7%]) and stair (27 of 90 [30.0%]) navigation than in daytime city (7 of 88 [8.0%]) and stair (19 of 96 [19.8%]) navigation. The overall VR disability score was associated with the National Eye Institute 25-item Visual Function Questionnaire Rasch score (R2 = 0.207). Conclusions and Relevance: These findings suggest that vision-related disability is associated with lighting condition and task in patients with glaucoma. Virtual reality may allow eye care professionals to understand the patients' perspectives on how visual impairment imparts disability in daily living and provide a new paradigm to augment the assessment of vision-related disability.

The Tenons' Layer Reposition Approach of Trabeculectomy: A Longitudinal Case Series of a Mixed Group of Glaucoma Patients.

SYNOPSIS: This 1-year prospective study demonstrated that the Tenon's layer reposition approach of trabeculectomy could achieve zero leakage rate, minimal rate of transient hypotony without compromising the surgical outcome. PURPOSE: The purpose of this study was to investigate the effectiveness and safety of a Tenon's layer reposition approach of trabeculectomy. METHODS: A prospective, noncomparative case series of 30 eyes of 30 Chinese patients with mixed types of glaucoma who underwent fornix-based trabeculectomy combined with intraoperative mitomycin C application. During the conjunctival flap closure, the Tenons' layer was identified, separated, and anchored on to the sclera surface with 8/0 vicryl, followed by conjunctival closure with 10/0 nylon as a separate layer. All patients were followed up for 1 year. Assessment including intraocular pressure (IOP), vertical cup-disc ratio measurement, best-corrected visual acuity, and visual field examination were performed before and after the operation. Qualified and complete success was defined as IOP of ≤21 mm Hg in 2 consecutive visits with or without medication, respectively. Outcomes were evaluated using scattered plot and Kaplan-Meier survival curve. RESULTS: Twenty-one eyes (70%) and 28 eyes (93.3%) achieved complete and partial success at 1 year, respectively. There was a significant reduction of IOP (28.5±9.6 to 15.5±2.6 mm Hg, P<0.001) and medication use (4.4±0.9 to 0.8±1.2 bottles/eye, P<0.001). There were no significant changes in best-corrected visual acuity, vertical cup-disc ratio, and visual field indices. No wound leak was identified throughout the study. The procedure did not induce significant astigmatic change. Other postoperative complications, including 2 eyes (6.7%) with transient hypotony and 1 eye (3.3%) required cataract surgery, were of relatively low rate. CONCLUSION: The Tenon's layer reposition approach of performing trabeculectomy is a safe and efficacious procedure for Chinese subjects with different types of glaucoma.

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

PURPOSE: To investigate whether progressive retinal nerve fiber layer (RNFL) thinning is predictive of progressive visual field (VF) loss in glaucoma. DESIGN: Prospective study. PARTICIPANTS: A total of 139 primary open-angle glaucoma patients (240 eyes) followed up for ≥5 years. METHODS: 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. MAIN OUTCOME MEASURES: The HRs of VF progression. RESULTS: 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. CONCLUSIONS: 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 its relevance 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.

Variability of Corneal Deformation Response in Normal and Keratoconic Eyes.

PURPOSE: To 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. METHODS: Three 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. RESULTS: Twelve 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). CONCLUSIONS: Corvis 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 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.

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.

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: measuring peripheral anterior synechia in glaucoma.

OBJECTIVE: To investigate the use of swept-source optical coherence tomography (OCT) for measuring the area and degree of peripheral anterior synechia (PAS) involvement in patients with angle-closure glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: Twenty-three eyes with PAS (detected by indentation gonioscopy) from 20 patients with angle-closure glaucoma (20 eyes had primary angle-closure glaucoma and 3 eyes had angle-closure glaucoma secondary to chronic anterior uveitis [n = 2] and Axenfeld-Rieger syndrome [n = 1]). METHODS: The anterior chamber angles were evaluated with indentation gonioscopy and imaged by swept-source OCT (Casia OCT, Tomey, Nagoya, Japan) in room light and in the dark using the "angle analysis" protocol, which was composed of 128 radial B-scans each with 512 A-scans (16-mm scan length). The area and degree of PAS involvement were measured in each eye after manual detection of the scleral spur and the anterior irido-angle adhesion by 2 masked observers. The interobserver variability of the PAS measurements was calculated. MAIN OUTCOME MEASURES: The agreement of PAS assessment by gonioscopy and OCT, the area and the degree of PAS involvement, and the intraclass correlation coefficient (ICC) of interobserver PAS measurements. RESULTS: The area of PAS (mean ± standard deviation) was 20.8 ± 16.9 mm(2) (range, 3.9-74.9 mm(2)), and the degree of PAS involvement was 186.5 ± 79.9 degrees (range, 42-314 degrees). There was no difference in the area of PAS (P = 0.90) and the degree of PAS involvement (P = 0.95) between images obtained in room light and in the dark. The interobserver ICCs were 0.99 (95% confidence interval [CI], 0.98-1.00) for the area of PAS and 0.99 (95% CI, 0.97-1.00) for the degree of PAS involvement. There was good agreement of PAS assessment between gonioscopy and OCT images (kappa = 0.79; 95% CI, 0.67-0.91). CONCLUSIONS: Swept-source OCT allows visualization and reproducible measurements of the area and degree of PAS involvement, providing a new paradigm for evaluation of PAS progression and risk assessment for development of angle-closure glaucoma. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

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.

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: a prospective analysis of age-related loss.

OBJECTIVE: To investigate age-related changes of the retinal nerve fiber layer (RNFL) imaged by a spectral-domain optical coherence tomography (OCT). DESIGN: Prospective, cross-sectional, and longitudinal studies. PARTICIPANTS: One hundred normal individuals were recruited for cross-sectional analysis, 35 of whom were randomly selected for longitudinal analysis. METHODS: The circumpapillary average and quadrant RNFL thicknesses were measured by the Cirrus HD-OCT. In the longitudinal study, participants were followed at 4-month intervals for a mean of 30 months (range, 24-41 months) for RNFL and visual field measurements. Cross-sectional RNFL data were analyzed with multiple linear regression models with adjustment of spherical error, optic disc area, and signal strength. Longitudinal RNFL measurements were analyzed with linear mixed models with fixed coefficients on follow-up duration, baseline RNFL thickness, spherical error, optic disc area, and signal strength. Factors influencing the rate of change of RNFL measurements were analyzed in the interaction terms with "duration" in the linear mixed models. MAIN OUTCOME MEASURES: Rates of change of average and quadrant RNFL thicknesses. RESULTS: In the cross-sectional analysis, significant negative correlations were found between age and average (-0.33 µm/year; P = 0.011), inferior (-0.45 µm/year; P = 0.037), and temporal (-0.31 µm/year; P = 0.046) RNFL thicknesses. In the longitudinal analysis, the mean rates of change of average, superior, and inferior RNFL thicknesses were -0.52 (95% confidence interval [CI], -0.86 to -0.17), -1.35 (95% CI, -2.05 to -0.65) and -1.25 µm/year (95% CI, -1.78 to -0.71), respectively, after adjusting for baseline RNFL thickness, spherical error, disc area, and signal strength. There was no detectable RNFL reduction in the nasal and temporal quadrants. The only significant factor influencing the rates of change of RNFL measurements was the baseline RNFL thickness. A greater baseline RNFL thickness was associated with a faster rate of change. CONCLUSIONS: Progressive, age-related decline of RNFL thickness can be detected with longitudinal OCT imaging. Rate estimates derived from trend analysis for detection of glaucomatous RNFL progression should be interpreted with reference to the normal ranges of age-related reduction, particularly when the baseline RNFL measurement is large.

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.

Evaluation of retinal nerve fiber layer progression in glaucoma: a comparison between spectral-domain and time-domain optical coherence tomography.

OBJECTIVE: To compare the performance of a spectral-domain optical coherence tomography (OCT) device and a time-domain OCT device to detect retinal nerve fiber layer (RNFL) progression in glaucoma patients. DESIGN: Prospective study. PARTICIPANTS: One hundred twenty-eight eyes of 81 glaucoma patients. METHODS: Patients were followed up at 4-month intervals for at least 24 months for RNFL imaging and visual field examination. Both eyes were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec, Inc., Dublin, CA) and the Stratus OCT (Carl Zeiss Meditec, Inc.) and underwent visual field testing at the same visit. Linear regression analyses between circumpapillary RNFL measurements (average, superior, and inferior RNFL thicknesses), visual field index (VFI), and follow-up time were performed. RNFL progression and RNFL improvement were identified when a significant negative or positive trend was detected, respectively. The agreement between the OCT instruments for progression detection was analyzed with κ statistics. MAIN OUTCOME MEASURES: Number of eyes with RNFL progression and improvement, agreement of progression detection between RNFL measurements and VFI, and rate of change of average RNFL thickness. RESULTS: Twenty-two eyes (19 patients) and 4 eyes (4 patients) had progression, and 0 and 5 eyes (5 patients) had improvement detected by the Cirrus HD-OCT and the Stratus OCT average RNFL measurements, respectively. The agreement for detection of RNFL progression was poor between the 2 OCT instruments (κ = 0.188, 0.027, and 0.267 for average, superior, and inferior RNFL thicknesses, respectively). The respective agreement between VFI and average RNFL thickness progression determined by the Cirrus HD-OCT and the Stratus OCT was 0.125 and 0.047. The rate of average RNFL thickness progression ranged between -1.52 µm/year and -5.03 µm/year for the Cirrus HD-OCT and between -2.22 µm/year and -7.60 µm/year for the Stratus OCT. CONCLUSIONS: The Cirrus HD-OCT outperformed the Stratus OCT in detecting more eyes with RNFL progression and fewer eyes with RNFL improvement. Because of reduced measurement variability, the Cirrus HD-OCT could detect changes in RNFL thickness sooner than the Stratus OCT. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.