title: Macular versus Retinal Nerve Fiber Layer Parameters for Diagnosing Manifest Glaucoma: A Systematic Review of Diagnostic Accuracy Studies.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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 comparative or randomized studies of OCT devices or OCT parameters and diagnostic strategies are essential.
authors.affiliation: Ophthalmology, Fondazione G.B. Bietti per lo studio e la ricerca in Oftalmolologia-IRCCS, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Oddone
authors.affiliation: Department of Neurosciences, Psychology, Drug Research and Children's Health, University of Florence, Florence, Italy. Electronic address: ersilia.lucenteforte@unifi.it.
authors.forename: Ersilia
authors.initials: E
authors.lastname: Lucenteforte
authors.affiliation: Ophthalmology, Fondazione G.B. Bietti per lo studio e la ricerca in Oftalmolologia-IRCCS, Rome, Italy.
authors.forename: Manuele
authors.initials: M
authors.lastname: Michelessi
authors.affiliation: Department of Translational Surgery and Medicine, Eye Clinic, University of Florence, Florence, Italy.
authors.forename: Stanislao
authors.initials: S
authors.lastname: Rizzo
authors.affiliation: Department of Surgical and Morphological Sciences, Section of Ophthalmology, University of Insubria, Varese-Como, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Donati
authors.affiliation: Ophthalmology, Fondazione G.B. Bietti per lo studio e la ricerca in Oftalmolologia-IRCCS, Rome, Italy.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Parravano
authors.affiliation: Department of Translational Surgery and Medicine, Eye Clinic, University of Florence, Florence, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Virgili
mesh_terms: D005901:Glaucoma / Q000175:diagnosis*; D006801:Humans; D008266:Macula Lutea / Q000473:pathology*; D009412:Nerve Fibers / Q000473:pathology*; D009898:Optic Disk / Q000473:pathology*; D015203:Reproducibility of Results; D012165:Retinal Ganglion Cells / Q000473:pathology*; D012680:Sensitivity and Specificity; D041623:Tomography, Optical Coherence