Intravitreal bevacizumab injection alone or combined with macular photocoagulation compared to macular photocoagulation as primary treatment of diabetic macular edema

Sandra P Jovanović; Vladimir Čanadanović; Ana Sabo; Zorka Grgić; Milena Mitrović; Dušan Rakić

doi:10.2298/5830

Sandra P Jovanović Clinic for Eye Diseases, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Vladimir Čanadanović Clinic for Eye Diseases, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Ana Sabo Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Zorka Grgić Clinic for Eye Diseases, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Milena Mitrović Endocrinology, Diabetes and Metabolic Disorders Clinic, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Dušan Rakić Department of Mathematics, Faculty of Technology, University of Novi Sad, Novi Sad, Serbia

DOI: https://doi.org/10.2298/5830

Keywords: diabetic retinopathy, macular edema, ophthalmologic surgical procedures, vascular endothelial growth factors, light coagulation, treatment outcome,

Abstract

Background/Aim. Within diabetic retinopathy (DR), diabetic macular edema (DME) is one of the leading causes of the loss of visual acuity. The aim of this study was to determine the efficacy of the intravitreal vascular endothelial growth factor (VEGF) inhibitor application alone or combined with macular focal/grid lasephotocoagulation compared with laser treatment alone. Methods. This prospective randomized clinical trial included 72 patients (120 treated eyes) with varying degrees of DR and DME. The DME treatment included intravitreal VEGF inhibitor bevacizumab (Avastin^®) application, with and without laser treatment. Bevacizumab (1.25 mg/0.05 mL) was administered intravitreally in 4–6-week intervals. Laser is applied 4–6 weeks after last dose of the drug as a part of combined treatment, or as the primary treatment. Results. The mean reduction in central macular thickness (CMT) for the eyes (n = 31) treated with bevacizumab alone was 162.23 µm, for the eyes (n = 53) treated with combined treatment the mean reduction in CMT was 124.24 µm, both statistically significant at p < 0.001. Laser macular photocolagulation as a part of combined treatment (in 53 eyes) significantly contributed to the CMT reduction, based on the paired t-test results (366.28 vs 323.0 µm at p < 0.05). In our study, the mean visual acuity improvement of 0.161 logMAR was achieved in the group of eyes treated with bevacizumab alone, and 0.093 logMAR in the group with combined treatment, both statistically significant at p < 0.05. The effect of laser photocolagulation alone on visual acuity and CMT was not statistically significant. Conclusion. Treatment with bevacizumab alone or within combined treatment is more effective in treating DME than conventional macular laser treatment alone, both anatomically and functionally.

Author Biography

Sandra P Jovanović, Clinic for Eye Diseases, Clinical Center of Vojvodina, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Ass. mr sci. med. dr Sandra Jovanović, asistent sa magistraturom, načelnik odeljenja bolesti zadnjeg segmenta oka

References

Klein R. Retinopathy in a population-based study. Trans Am Ophthalmol Soc 1992; 90: 561−94.

Kempen JH, O'Colmain BJ, Leske MC, Haffner SM, Klein R, Moss SE, et al. The prevalence of diabeticretinopathy among adults in the United States. Arch Ophthalmol. 2004; 122(4): 552−63.

Orchard TJ, Dorman JS, Maser RE, Becker DJ, Drash AL, Ellis D, et al. Prevalence of complications in IDDM by sex and dura-tion. Pittsburgh Epidemiology of Diabetes Complications Study II. Diabetes 1990; 39(9): 1116−24.

Girach A, Lund-Andersen H. Diabetic macular oedema: a clinical overview. Int J Clin Pract 2007; 61(1): 88−97.

Williams R, Airey M, Baxter H, Forrester J, Kennedy-Martin T, Girach A. Epidemiology of diabetic retinopathy and macular oedema: a systematic review. Eye 2004; 18(10): 963−83.

Gardner TW, Antonetti DA, Barber AJ, LaNoue KF, Levison SW. Diabetic retinopathy: more than meets the eye. Surv Ophthal-mol 2002; 47(Suppl 2): S253−62.

Cai J, Boulton M. The pathogenesis of diabetic retinopathy: old concepts and new questions. Eye (Lond) 2002; 16(3): 242−60.

Ferrara N. Role of vascular endothelial growth factor in phys-iologic and pathologic angiogenesis: therapeutic implications. Semin Oncol 2002; 29(6 Suppl 16): 10−4.

Takahashi H, Shibuya M. The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiolog-ical and pathological conditions. Clin Sci 2005; 109(3): 227−41.

Scott IU, Edwards AR, Beck RW, Bressler NM, Chan CK, Elman MJ, et al. A phase II randomized clinical trial of intravitreal bevacizumab for diabetic macular edema. Ophthalmology 2007; 114(10): 1860−7.

Fong DS, Strauber SF, Aiello LP, Beck RW, Callanan DG, Danis RP, et al. Writing Committee for the Diabetic Retinopathy Clinical Research Network. Comparison of the modified Early Treatment Diabetic Retinopathy Study and mild macular grid laser photocoagulation strategies for diabetic macular edema. Arch Ophthalmol 2007; 125(4): 469−80.

Wilkinson CP, Ferris FL, Klein RE, Lee PP, Agardh CD, Davis M, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003; 110(9): 1677−82.

Faghihi H, Esfahani MR, Harandi ZA, Madani SH. Intravitreal bevacizumab vs. combination of intravitreal bevacizumab plus macular photocoagulation in clinically significant diabetic macular edema: 6 months results of a randomized clinical trial. Iranian J Ophthalmol 2010; 22(1): 21−6.

Rajendram R, Fraser-Bell S, Kaines A, Michaelides M, Hamilton RD, Esposti SD, et al. A 2-year prospective randomized controlled trial of intravitreal bevacizumab or laser therapy (BOLT) in the management of diabetic macular edema: 24-month data: report 3. Arch Ophthalmol 2012; 130(8): 972−9.

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(9): 999−1005.

Kook D, Wolf A, Kreutzer T, Neubauer A, Strauss R, Ulbig M, et al. Long-term effect of intravitreal bevacizumab (avastin) in patients with chronic diffuse diabetic macular edema. Retina 2008; 28(8): 1053−60.

Mehta S, Blinder KJ, Shah GK, Kymes SM, Schlief SL, Grand MG. Intravitreal bevacizumab for the treatment of refractory dia-betic macular edema. Ophthalmic Surg Lasers Imaging 2010; 41(3): 323−9.

Roh MI, Byeon SH, Kwon OW. Repeated intravitreal injection of bevacizumab for clinically significant diabetic macular edema. Retina 2008; 28(9): 1314−8.

Arevalo J, Fromow-Guerra J, Quiroz-Mercado H, Sanchez JG, Wu L, Maia M, et al. Primary intravitreal bevacizumab (Avastin) for diabetic macular edema: results from the Pan-American Col-laborative Retina Study Group at 6-month follow-up. Oph-thalmology 2007; 114(4): 743−50.

Kumar A, Sinha S. Intravitreal bevacizumab (Avastin) treatment of diffuse diabetic macular edema in an Indian population. In-dian J Ophthalmol 2007; 55(6): 451−5.

Lee SJ, Kim ET, Moon SY. Intravitreal bevacizumab alone ver-sus combined with macular photocoagulation in diabetic mac-ular edema. Korean J Ophthalmol 2011; 25(5): 299−304.