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.

Wide-field Trend-based Progression Analysis of Combined Retinal Nerve Fiber Layer and Ganglion Cell Inner Plexiform Layer Thickness: A New Paradigm to Improve Glaucoma Progression Detection.

OBJECTIVE: Evaluation of glaucoma progression with OCT has been centered on the analysis of progressive retinal nerve fiber layer (RNFL) thinning over the parapapillary region and/or progressive ganglion cell inner plexiform layer (GCIPL) thinning over the macula. We investigated (1) whether combining the RNFL and GCIPL as a single layer (i.e., RNFL-GCIPL) for wide-field progression analysis outperforms wide-field progression analysis of the RNFL or the GCIPL, and (2) whether eyes with progressive RNFL-GCIPL thinning are at risk of visual field (VF) progression. DESIGN: Prospective, longitudinal study. PARTICIPANTS: A total of 440 eyes from 236 glaucoma patients; 98 eyes from 49 healthy individuals. METHODS: OCT RNFL/GCIPL/RNFL-GCIPL thickness and VF measurements were obtained at ∼4-month intervals for ≥3 years. Progressive changes of the RNFL/GCIPL/RNFL-GCIPL thicknesses were analyzed over a wide field (12×9 mm2) covering the parapapillary region and the macula with trend-based progression analysis (TPA) controlled at a false discovery rate of 5%. VF progression was determined by the Early Manifest Glaucoma Trial criteria. MAIN OUTCOME MEASURES: Proportions of eyes with progressive RNFL/GCIPL/RNFL-GCIPL thinning; hazard ratios (HRs) for development of VF progression. RESULTS: More eyes showed progressive RNFL-GCIPL thinning (127 eyes; 28.9%, 95% confidence interval [CI]: 23.9%-33.8%) than progressive RNFL thinning (74 eyes; 16.8%, 95% CI: 13.1%-20.6%) and progressive GCIPL thinning (26 eyes; 5.9%, 95% CI: 3.7%-8.1%) in the glaucoma group over the study follow-up. Progressive RNFL-GCIPL thinning was almost always detected before or simultaneously with progressive RNFL thinning or progressive GCIPL thinning. The specificity of TPA (estimated from the healthy group) for detection of progressive RNFL-GCIPL thinning, progressive RNFL thinning, and progressive GCIPL thinning was 83.7% (95% CI: 74.9%-92.4%), 94.9% (95% CI: 90.6%-99.2%), and 96.9% (95% CI: 93.5%-100.0%), respectively. Eyes with progressive RNFL-GCIPL thinning had a higher risk to develop possible (HR: 2.4, 95% CI: 1.2-5.0) or likely (HR: 4.6, 95% CI: 1.5-14.0) VF progression, with adjustment of covariates, compared with eyes without progressive RNFL-GCIPL thinning. CONCLUSIONS: Progression analysis of RNFL-GCIPL thickness reveals a significant portion of progressing eyes that neither progression analysis of RNFL thickness nor GCIPL thickness would identify. Wide-field progression analysis of RNFL-GCIPL thickness is effective to inform the risk of VF progression in glaucoma patients.

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.