title: Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy.
abstract: OBJECTIVE
  To evaluate the predictive value of microaneurysm (MA) formation rate concerning the development of clinically significant macular edema (CSME) in patients with mild-to-moderate nonproliferative diabetic retinopathy as evaluated by an automated analysis of central field fundus 30° photographs.
  
  
  METHODS
  Two hundred and eighty-seven eyes were included in the study. Photographs obtained at Day 0, at 6, and 12 months were analyzed using the RetmarkerDR software (Critical Health SA) in a masked manner, and the MA formation rate was documented. A threshold of a calculated MA formation rate of 2 or more was chosen to consider a patient "positive." The ability to predict CSME development was then calculated for a period of up to 5 years. HbA1c values, blood pressure, or duration of diabetes were also evaluated.
  
  
  RESULTS
  The study population consisted of 89 male and 59 female patients with a mean age of 57.6 years, a mean HbA1c of 7.8, and a mean duration of diabetes of 12.3 years. Forty-seven of 287 eyes (16.4%) developed CSME during follow-up. An increased MA formation rate of >2 MA was clearly associated with development of CSME. Using the automated analysis and a threshold of 2 or more new MA, the authors were able to identify 70.2% of the eyes that developed CSME during follow-up ("true positive") and using a threshold of up to 2 new MA, 71.7% of the patients that did not develop CSME ("true negative"). No significant differences concerning baseline and 1-year HbA1c levels within patient eyes that developed CSME compared with patient eyes below or over the calculated threshold of 2 MA (P = 0.554 and P = 0.890, respectively) were seen. The positive and negative predictive value was calculated to be 33% versus 92.5%, sensitivity was 70%, and specificity was 72%.
  
  
  CONCLUSIONS
  Using the RetmarkerDR software, the authors were able to identify patients with higher risk to develop CSME during follow-up using a threshold of 2 or more MA formation rate. Together with the high negative predictive value, the automated analysis may help to determine the individual risk of a patient to develop sight-threatening complications related to diabetic retinopathy and schedule individual screening intervals.
authors.affiliation: *Department of Ophthalmology, Ludwig-Maximilians-University, Munich, Germany; †Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany; and ‡Critical Health SA, Coimbra, Portugal.
authors.forename: Christos
authors.initials: C
authors.lastname: Haritoglou
authors.forename: Marcus
authors.initials: M
authors.lastname: Kernt
authors.forename: Aljoscha
authors.initials: A
authors.lastname: Neubauer
authors.forename: Joachim
authors.initials: J
authors.lastname: Gerss
authors.forename: Carlos Manta
authors.initials: CM
authors.lastname: Oliveira
authors.forename: Anselm
authors.initials: A
authors.lastname: Kampik
authors.forename: Michael
authors.initials: M
authors.lastname: Ulbig
mesh_terms: D000328:Adult; D000368:Aged; D000783:Aneurysm / Q000097:blood / Q000175:diagnosis*; D015415:Biomarkers; D001794:Blood Pressure; D003930:Diabetic Retinopathy / Q000097:blood / Q000175:diagnosis*; D018450:Disease Progression; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008269:Macular Edema / Q000097:blood / Q000175:diagnosis*; D008297:Male; D008875:Middle Aged; D012171:Retinal Vessels / Q000473:pathology*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human