Macular versus Retinal Nerve Fiber Layer Parameters for Diagnosing Manifest Glaucoma: A Systematic Review of Diagnostic Accuracy Studies

Abstract

Macular parameters have been proposed as an alternative to retinal nerve fiber layer (RNFL) parameters to diagnose glaucoma. Comparing the diagnostic accuracy of macular parameters, specifically the ganglion cell complex (GCC) and ganglion cell inner plexiform layer (GCIPL), with the accuracy of RNFL parameters for detecting manifest glaucoma is important to guide clinical practice and future research. Studies using spectral domain optical coherence tomography (SD OCT) and reporting macular parameters were included if they allowed the extraction of accuracy data for diagnosing manifest glaucoma, as confirmed with automated perimetry or a clinician's optic nerve head (ONH) assessment. Cross-sectional cohort studies and case-control studies were included. The QUADAS 2 tool was used to assess methodological quality. Only direct comparisons of macular versus RNFL parameters (i.e., in the same study) were conducted. Summary sensitivity and specificity of each macular or RNFL parameter were reported, and the relative diagnostic odds ratio (DOR) was calculated in hierarchical summary receiver operating characteristic (HSROC) models to compare them. Thirty-four studies investigated macular parameters using RTVue OCT (Optovue Inc., Fremont, CA) (19 studies, 3094 subjects), Cirrus OCT (Carl Zeiss Meditec Inc., Dublin, CA) (14 studies, 2164 subjects), or 3D Topcon OCT (Topcon, Inc., Tokyo, Japan) (4 studies, 522 subjects). Thirty-two of these studies allowed comparisons between macular and RNFL parameters. Studies generally reported sensitivities at fixed specificities, more commonly 0.90 or 0.95, with sensitivities of most best-performing parameters between 0.65 and 0.75. For all OCT devices, compared with RNFL parameters, macular parameters were similarly or slightly less accurate for detecting glaucoma at the highest reported specificity, which was confirmed in analyses at the lowest specificity. Included studies suffered from limitations, especially the case-control study design, which is known to overestimate accuracy. However, this flaw is less relevant as a source of bias in direct comparisons conducted within studies. With the use of OCT, RNFL parameters are still preferable to macular parameters for diagnosing manifest glaucoma, but the differences are small. Because of high heterogeneity, direct comparativeor randomized studies of OCT devices or OCT parameters and diagnostic strategies are essential.