title: Investigation of Adaptive Optics Imaging Biomarkers for Detecting Pathological Changes of the Cone Mosaic in Patients with Type 1 Diabetes Mellitus.
abstract: OBJECTIVE
  To investigate a set of adaptive optics (AO) imaging biomarkers for the assessment of changes of the cone mosaic spatial arrangement in patients with type 1 diabetes mellitus (DM1).
  
  
  METHODS
  16 patients with ≥20/20 visual acuity and a diagnosis of DM1 in the past 8 years to 37 years and 20 age-matched healthy volunteers were recruited in this study. Cone density, cone spacing and Voronoi diagrams were calculated on 160x160 μm images of the cone mosaic acquired with an AO flood illumination retinal camera at 1.5 degrees eccentricity from the fovea along all retinal meridians. From the cone spacing measures and Voronoi diagrams, the linear dispersion index (LDi) and the heterogeneity packing index (HPi) were computed respectively. Logistic regression analysis was conducted to discriminate DM1 patients without diabetic retinopathy from controls using the cone metrics as predictors.
  
  
  RESULTS
  Of the 16 DM1 patients, eight had no signs of diabetic retinopathy (noDR) and eight had mild nonproliferative diabetic retinopathy (NPDR) on fundoscopy. On average, cone density, LDi and HPi values were significantly different (P<0.05) between noDR or NPDR eyes and controls, with these differences increasing with duration of diabetes. However, each cone metric alone was not sufficiently sensitive to discriminate entirely between membership of noDR cases and controls. The complementary use of all the three cone metrics in the logistic regression model gained 100% accuracy to identify noDR cases with respect to controls.
  
  
  CONCLUSIONS
  The present set of AO imaging biomarkers identified reliably abnormalities in the spatial arrangement of the parafoveal cones in DM1 patients, even when no signs of diabetic retinopathy were seen on fundoscopy.
authors.affiliation: Fondazione G.B. Bietti IRCCS, Via Livenza 3, 00198, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Lombardo
authors.affiliation: Fondazione G.B. Bietti IRCCS, Via Livenza 3, 00198, Rome, Italy.
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Parravano
authors.affiliation: Fondazione G.B. Bietti IRCCS, Via Livenza 3, 00198, Rome, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Serrao
authors.affiliation: Fondazione G.B. Bietti IRCCS, Via Livenza 3, 00198, Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ziccardi
authors.affiliation: Fondazione G.B. Bietti IRCCS, Via Livenza 3, 00198, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Giannini
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto per i Processi Chimico-Fisici (CNR-IPCF), Viale Stagno D'Alcontres 37, 98158, Messina, Italy.|Vision Engineering Italy srl, Via Adda 7, 00198, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lombardo
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D061848:Optical Imaging / Q000379:methods*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers