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 < 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.

1.
Harris MI: Diabetes in America: epidemiology and scope of the problem. Diabetes Care 1998;21(suppl 3):C11-C14.
2.
Claessen H, Genz J, Bertram B, Trautner C, Giani G, Zöllner I, et al: Evidence for a considerable decrease in total and cause-specific incidences of blindness in Germany. Eur J Epidemiol 2012;27:519-524.
3.
Wormald R, Henshaw K, Smeeth L: Evidence-Based Ophthalmology. London, BMJ Books, 2008.
4.
Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol 1985;103:1796-1806.
5.
Haritoglou C, Kook D, Neubauer A, Wolf A, Priglinger S, Strauss R, et al: Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema. Retina 2006;26:999-1005.
6.
Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, et al: The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 2011;118:615-625.
7.
Do DV, Nguyen QD, Boyer D, Schmidt-Erfurth U, Brown DM, Vitti R, et al: One-year outcomes of the Da Vinci Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology 2012;119:1658-1665.
8.
Cunha-Vaz J: Characterization and relevance of different diabetic retinopathy phenotypes. Dev Ophthalmol 2007;39:13-30.
9.
Nunes S, Pires I, Rosa A, Duarte L, Bernardes R, Cunha-Vaz JE: Microaneurysm turnover is a biomarker for diabetic retinopathy progression to clinically significant macular edema: findings for type 2 diabetics with nonproliferative retinopathy. Ophthalmologica 2009;223:292-297.
10.
Haritoglou C, Kernt M, Neubauer A, Gerss J, Oliveira CM, Kampik A, et al: Microaneurysm formation rate as a predictive marker for progression to clinically significant macular edema in nonproliferative diabetic retinopathy. Retina 2014;34:157-164.
11.
Ribeiro ML, Nunes SG, Cunha-Vaz JG: Microaneurysm turnover at the macula predicts risk of development of clinically significant macular edema in persons with mild nonproliferative diabetic retinopathy. Diabetes Care 2012;36:1254-1259.
12.
Kohner EM, Sleightholm M: Does microaneurysm count reflect severity of early diabetic retinopathy? Ophthalmology 1986;93:586-589.
13.
Reznicek L, Kernt M, Haritoglou C, Ulbig M, Kampik A, Neubauer AS: Correlation of leaking microaneurysms with retinal thickening in diabetic retinopathy. Int J Ophthalmol 2011;4:269-271.
14.
Vincze P, Madácsy L, Petheö I, Brooser G: Prognostic significance of retinal microaneurysm number and localization in type-1 diabetes mellitus (in Hungarian). Orv Hetil 2001;142:2015-2020.
15.
Sjølie AK, Klein R, Porta M, Orchard T, Fuller J, Parving HH, et al: Retinal microaneurysm count predicts progression and regression of diabetic retinopathy. Post-hoc results from the DIRECT Programme. Diabet Med 2011;28:345-351.
16.
Hellstedt T, Immonen I: Disappearance and formation rates of microaneurysms in early diabetic retinopathy. Br J Ophthalmol 1996;80:135-139.
17.
Klein R, Meuer SM, Moss SE, Klein BE: Retinal microaneurysm counts and 10-year progression of diabetic retinopathy. Arch Ophthalmol 1995;113:1386-1391.
18.
Lee SN, Chhablani J, Chan CK, Wang H, Barteselli G, El-Emam S, et al: Characterization of microaneurysm closure after focal laser photocoagulation in diabetic macular edema. Am J Ophthalmol 2013;155:905-912.e2.
19.
Sachdev N, Gupta V, Abhiramamurthy V, Singh R, Gupta A: Correlation between microaneurysm closure rate and reduction in macular thickness following laser photocoagulation of diabetic macular edema. Eye 2007;22:975-977.
20.
Kernt M, Cserhati S, Seidensticker F, Liegl R, Kampik A, Neubauer A, et al: Improvement of diabetic retinopathy with intravitreal ranibizumab. Diabetes Res Clin Pract 2013;100:e11-e13.
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