title: Microaneurysm turnover in diabetic retinopathy assessed by automated RetmarkerDR image analysis--potential role as biomarker of response to ranibizumab treatment.
abstract: OBJECTIVE
  To evaluate the influence of a ranibizumab treatment on microaneurysm (MA) turnover in diabetic retinopathy.
  
  
  METHODS
  Sixty-nine eyes were included in this retrospective study. We compared a group of 33 eyes with ranibizumab treatment for diabetic macular edema to 36 eyes with nonproliferative diabetic retinopathy only. Nonmydriatic ultra-widefield scanning laser ophthalmoscopy (Optomap) images were obtained at a mean 4.76 ± 1.69 days prior to the first ranibizumab injection (baseline) and again 35.94 ± 2.44 days after the third consecutive injection in a 4-week interval. In untreated controls, images were obtained at baseline and 97.81 ± 3.16 days thereafter. Images were analyzed using the RetmarkerDR software (Critical Health SA, Coimbra, Portugal), and the turnover of MAs was documented and analyzed. Thereafter, MA turnover was correlated with central retinal thickness (CRT) as assessed by OCT.
  
  
  RESULTS
  At baseline, patients in the treatment group had 5.64 ± 0.75 MAs. One month after 3 ranibizumab injections, measured MAs decreased to 4.03 ± 0.66. In the untreated control group, the initial number of 3.36 ± 0.6 MAs remained almost unchanged over 3-4 months (2.89 ± 0.57 MAs). Dynamic analysis showed that after ranibizumab treatment 3.06 ± 0.5 new MAs appeared, while 5.09 ± 0.79 disappeared. In the control group, 2.11 ± 0.4 new MAs appeared and 2.61 ± 0.48 disappeared. MA turnover was significantly higher with ranibizumab compared to the control group (8.15 ± 1.14 vs. 4.72 ± 0.81, p < 0.001). Consistently, CRT decreased from 444 to 330 µm in the ranibizumab group, while there was no change in the control group (291 vs. 288 µm).
  
  
  CONCLUSIONS
  The treatment of macular edema using ranibizumab does not only reduce macular thickness, but also has an impact on the turnover of MAs in diabetic retinopathy. RetmarkerDR analysis showed that more pre-existent MAs disappeared than new MAs developed, and the absolute number of MAs also decreased.
authors.affiliation: Department of Ophthalmology, Ludwig Maximilian University, Munich, Germany.
authors.forename: Simon F
authors.initials: SF
authors.lastname: Leicht
authors.forename: Marcus
authors.initials: M
authors.lastname: Kernt
authors.forename: Aljoscha
authors.initials: A
authors.lastname: Neubauer
authors.forename: Armin
authors.initials: A
authors.lastname: Wolf
authors.forename: Carlos Manta
authors.initials: CM
authors.lastname: Oliveira
authors.forename: Michael
authors.initials: M
authors.lastname: Ulbig
authors.forename: Christos
authors.initials: C
authors.lastname: Haritoglou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000783:Aneurysm / Q000175:diagnosis*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015415:Biomarkers; D003930:Diabetic Retinopathy / Q000175:diagnosis / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009887:Ophthalmoscopy; D000069579:Ranibizumab; D012160:Retina / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology*; D012189:Retrospective Studies; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab