title: Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema.
abstract: OBJECTIVE
  Biomarkers that predict future visual acuity (VA) in eyes with baseline diabetic macular edema (DME) would substantively improve risk assessment, management decisions, and selection of eyes for clinical studies targeting DME.
  
  
  OBJECTIVE
  To determine whether baseline or early change in the novel spectral domain-optical coherence tomography (SD-OCT) parameter disorganization of the retinal inner layers (DRIL) is predictive of VA in eyes with center-involved DME.
  
  
  METHODS
  At a tertiary care referral center for diabetic eye disease, a retrospective, longitudinal cohort study obtained demographics, VA, and SD-OCT images from baseline, 4-month, and 8-month visits in 96 participants (120 eyes) with diabetes mellitus and baseline center-involved DME (SD-OCT central subfield thickness, ≥ 320 µm for men and ≥ 305 µm for women). Exclusion criteria included substantial media opacity, cataract surgery within 6 months, and nondiabetic retinal pathology affecting VA. On SD-OCT, the 1-mm-wide retinal area centered on the fovea was evaluated by masked graders for DRIL extent, cysts, hyperreflective foci, microaneurysms, cone outer segment tip visibility, and external limiting membrane or photoreceptor disruption and reflectivity.
  
  
  METHODS
  Visual acuity and SD-OCT-derived retinal morphology.
  
  
  RESULTS
  Greater DRIL extent at baseline correlated with worse baseline VA (point estimate, 0.04; 95% CI, 0.02-0.05 per 100 µm; P < .001). An increase in DRIL during 4 months was associated with VA worsening at 8 months (point estimate, 0.03; 95% CI, 0.02-0.05 per 100 µm; P < .001). A multivariate model that included a 4-month change in VA, DRIL, and external limiting membrane disruption was predictive of an 8-month VA change (r = 0.80). Each approximately 300-µm DRIL increase during 4 months predicted a 1-line, 8-month VA decline. When DRIL increased at least 250 µm at 4 months, no eyes had VA improvement of at least 1 line at 8 months. When DRIL decreased at least 250 µm at 4 months, no eyes had VA decline of at least 1 line at 8 months, and 77.7% had VA improvement of at least 1 line.
  
  
  CONCLUSIONS
  Disorganization of the retinal inner layers in the 1-mm foveal area is associated with VA, and change in DRIL predicts future change in VA. Early change in DRIL prospectively identifies eyes with a high likelihood of subsequent VA improvement or decline. Therefore, DRIL warrants further study as a robust, readily obtained, and noninvasive biomarker of future VA response in eyes with DME.
authors: Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts2Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors: Jennifer K
authors: JK
authors: Sun
authors: Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts3currently a medical student at Harvard Medical School, Boston, Massachusetts.
authors: Michael M
authors: MM
authors: Lin
authors: Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts4Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.
authors: Jan
authors: J
authors: Lammer
authors: Department of Ophthalmology and Optometry, Medical University of Vienna, Vienna, Austria.
authors: Sonja
authors: S
authors: Prager
authors: currently a medical student at Boston University School of Medicine, Boston, Massachusetts.
authors: Rutuparna
authors: R
authors: Sarangi
authors: Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts2Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors: Paolo S
authors: PS
authors: Silva
authors: Beetham Eye Institute, Joslin Diabetes Center, Boston, Massachusetts2Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.
authors: Lloyd Paul
authors: LP
authors: Aiello
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003930:Diabetic Retinopathy / Q000503:physiopathology*; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D006801:Humans; D008269:Macular Edema / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012160:Retina / Q000473:pathology*; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D014786:Vision Disorders / Q000503:physiopathology*; D014792:Visual Acuity / Q000502:physiology*
chemical_list: D015415:Biomarkers