Retinal Nerve Fiber Layer Optical Texture Analysis: Detecting Axonal Fiber Bundle Defects in Patients with Ocular Hypertension.

PURPOSE: To apply retinal nerve fiber layer (RNFL) optical texture analysis (ROTA) to investigate the prevalence, patterns, and risk factors of RNFL defects in patients with ocular hypertension (OHT) who showed normal optic disc and RNFL configuration in clinical examination, normal RNFL thickness on OCT analysis, and normal visual field (VF) results. DESIGN: Cross-sectional study. PARTICIPANTS: Six hundred eyes of 306 patients with OHT. METHODS: All participants underwent clinical examination of the optic disc and RNFL, OCT RNFL imaging, and 24-2 standard automated perimetry. To detect RNFL defects, ROTA was applied. The risk score for glaucoma development was calculated according to the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study (OHTS-EGPS) risk prediction model. Risk factors associated with RNFL defects were analyzed using multilevel logistic regression analysis. MAIN OUTCOME MEASURES: Prevalence of RNFL defects. RESULTS: The average intraocular pressure (IOP) measured from 3 separate visits within 6 months was 24.9 ± 1.8 mmHg for the eye with higher IOP and 23.7 ± 1.7 mmHg for the eye with lower IOP; the respective central corneal thicknesses were 568.7 ± 30.8 µm and 568.8 ± 31.2 µm. Of 306 patients with OHT, 10.8% (33 patients, 37 eyes) demonstrated RNFL defects in ROTA in at least 1 eye. Of the 37 eyes with RNFL defects, the superior arcuate bundle was the most frequently involved (62.2%), followed by the superior papillomacular bundle (27.0%) and the inferior papillomacular bundle (21.6%). Papillofoveal bundle defects were observed in 10.8% of eyes. The smallest RNFL defect spanned 0.0° along Bruch's membrane opening margin, whereas the widest RNFL defect extended over 29.3°. Age (years) (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.03-1.13), VF pattern standard deviation (decibels [dB]) (OR, 1.82; 95% CI, 1.01-3.29), cup volume (mm3) (OR, 1.24; 95% CI, 1.01-1.53), and the OHTS-EPGS risk score (OR, 1.04; 95% CI, 1.01-1.07) were associated with RNFL defects. CONCLUSIONS: A considerable proportion of patients with OHT who showed no signs of optic disc and RNFL thickness abnormalities on clinical and OCT examination exhibited RNFL defects on ROTA. Axonal fiber bundle defects on ROTA may represent the earliest discernible sign of glaucoma in the glaucoma continuum. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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.

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).

Factors Associated With Long-term Intraocular Pressure Fluctuation in Primary Angle Closure Disease: The CUHK PACG Longitudinal (CUPAL) Study.

PURPOSE: To determine the demographic, ocular, and systemic factors associated with long-term intraocular pressure (IOP) fluctuation in primary angle closure disease (PACD). METHODS: This prospective cohort study included 422 PACD eyes from 269 Chinese patients, including 274 primary angle closure glaucoma (PACG) eyes and 152 primary angle closure/primary angle closure suspect (PAC/PACS) eyes. Long-term IOP fluctuation defined as the SD of all IOP measurements over 2 years (at least 5 measurements in total). Chinese patients with PACD were recruited and followed up 3 monthly. Eyes with IOP-lowering surgery or lens extraction performed within the 2-year study period were excluded. Patient demographics, received treatments, ocular biometry, retinal nerve fiber layer thickness, and systemic factors (eg, hypertension, smoking) were evaluated. Generalized estimating equations adjusting for inter-eye correlation were used to determine the associations. RESULTS: Eyes with PACG had significantly higher IOP fluctuation than PAC/PACS (2.4±1.2 versus 2.1±0.9 mm Hg; P=0.04). In the multivariate analysis with PACG eyes, higher baseline IOP (P<0.001), greater number of IOP-lowering medications (P<0.001), previous trabeculectomy (P=0.002), and current smoking (P=0.03) were significantly associated with larger IOP fluctuation, whereas diabetes mellitus was associated with lower IOP fluctuation (P=0.03). Among PAC/PACS eyes, younger age group (P<0.001), male sex (P=0.002), and higher baseline IOP (P<0.001) were significantly associated with larger IOP fluctuation. CONCLUSIONS: PACG eyes have greater IOP fluctuation than PAC/PACS eyes. Certain demographic, ocular, and systemic factors are associated with IOP fluctuation in PACD eyes.

Circadian Intraocular Pressure Fluctuation and Disease Progression in Primary Angle Closure Glaucoma.

PURPOSE: To document the continuous circadian intraocular pressure (IOP) fluctuation using a contact lens sensor during normal daily activities, and to study the relationship between IOP fluctuation and disease progression in primary angle closure glaucoma (PACG) eyes. METHODS: Circadian IOP fluctuations were recorded by Sensimed Triggerfish sensors in 25 PACG eyes. The sensor output signals were smoothed using B-spline smoothing transform and described by functional data analysis. Glaucoma progression was documented with serial changes in mean deviation (MD) and visual field index (VFI) in Humphrey automated perimetry and retinal nerve fiber layer (RNFL) thickness. The signals were compared between the progressive and stable groups by permutation tests on functional t-statistic. RESULTS: Statistically significant differences were found from 2200 to 2300 and from 0700 to 0800 in gradients of the IOP fluctuation curve, as well as from 2300 to 2400 and 0800 to 0900 in curvatures of the IOP fluctuation curves, between the progressive MD and stable MD groups (P < 0.05). Significant gradient differences were also found from 1500 to 1600 and 0600 to 0800 between the progressive VFI and stable VFI groups, and from 2400 to 0100 and 0200 to 0300 between the progressive RNFL and stable RNFL groups (P < 0.05). CONCLUSIONS: Significant differences in circadian IOP fluctuation between progressive and stable PACG eyes were identified. Large IOP fluctuations may be associated with disease progression in PACG eyes.