Microaneurysm turnover in diabetic retinopathy assessed by automated RetmarkerDR image analysis - potential role as biomarker of response to ranibizumab treatment

PURPOSE 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 \textless 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). CONCLUSION 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