Old and New Methods of Glaucoma Diagnosis Using Spectral-Domain Optical Coherence Tomography: Testing Limitations of Older Retinal Nerve Fiber Layer Thickness Measurements and Diagnostic Potential of Newer Retinal Volume Measurements

Abstract

Purpose: Optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness measurements are a reproducible and quantitative diagnostic modality widely used for glaucoma evaluations, but a high rate of testing artifacts limits its clinical utility. In Part I of this thesis, we aimed to characterize artifact types and assess artifact rates in two-dimensional (2D) RNFL thickness measurements obtained by the Spectralis OCT machine (Heidelberg Engineering, Heidelberg, Germany), as well as to determine patient factors and eye conditions associated with a higher artifact prevalence. In Part II of this thesis, we aimed to compare a new parameter, peripapillary retinal volume (RV), with the traditional 2D RNFL thickness parameter for diagnostic capability and artifact rates.

Methods: Part I: The prevalence of 12 artifact types were described in this retrospective, cross sectional review of 2313 eye scans from 1188 patients who underwent a complete eye examination with Spectralis OCT scanning during the period of September 2009 to July 2013. Generalized estimating equations model was used to analyze associations between increased artifact prevalence and 10 patient characteristics, including age, sex, race, visual acuity, refractive error, astigmatism, cataract status, glaucoma staging, visual field reliability, and glaucoma diagnosis.

Part II: This is a retrospective, cross-sectional review. A total of 180 subjects [113 open angle glaucoma (OAG) and 67 normal participants] had spectral domain optical coherence tomography (OCT) volume scans and RNFL thickness measurements (Spectralis, Heidelberg Engineering, Heidelberg, Germany). Peripapillary RV values were calculated using a custom-designed program with 4 different sized circumpapillary annuli (CA): CA1 had circle diameters of 2.5 and 3.5 mm; CA2, 3 and 4 mm; CA3, 3.5 and 4.5 mm; and CA4, 4 and 5 mm. Area under the receiver operating characteristic (AUROC) curves, sensitivity, and specificity were calculated for global, quadrant, and octant regions for RV (CA1 – CA4) and RNFL thickness. Pair-wise comparisons were conducted between RV and RNFL measurements. Artifacts rates were determined.

Results: Part I: A total of 1070 or 46.3% of the 2313 2D eye scans had at least one artifact. De-centration error was the most common artifact (27.8%), followed by posterior vitreous detachment artifacts (14.4%). Visual acuity of less than 20/40 (p<0.0001), presence of moderate to severe cataracts (p<0.0001), advanced stage of glaucoma (p<0.0001), and a diagnosis of open angle glaucoma (p=0.0003) were associated with increased prevalence of artifacts.

Part II: Of the 180 study subjects who had 3D eye scans, mean age was 62.6 ± 15.4 years and 41.7% were male. Among RV measurements, best diagnostic performances were for the smallest two annuli for inferior RV (CA1 0.964, CA2 0.955). Of the 4 annuli, the smallest CA1 had the highest diagnostic performance. Of specific regions, the inferior RV quadrant had the highest performance across CA1 to CA4. Peripapillary RV had similar diagnostic capability compared to RNFL thickness (p > 0.05). The artifact rate per B-scan for RV was 6.0%, and for 2D RNFL thickness scans was 32.2%.

Conclusions: Clinicians should first assess scans for artifacts and pay attention to patient characteristics associated with a higher prevalence of artifacts before making therapeutic decisions based on RNFL thickness measurements. Meanwhile, the diagnostic capability of RV could be equal to that of RNFL thickness for diagnosing perimetric OAG, with fewer artifacts. RV may be a useful novel parameter in the evaluation of perimetric glaucoma.