title: Effect of leaking perifoveal microaneurysms on resolution of diabetic macular edema treated by combination therapy using anti-vascular endothelial growth factor and short pulse focal/grid laser photocoagulation.
abstract: OBJECTIVE
  The effect of combination therapy using intravitreal ranibizumab (IVR) injections and short pulse focal/grid laser photocoagulation was evaluated for the treatment of diabetic macular edema (DME).
  
  
  METHODS
  The current investigation was a preliminary single-arm, open-label, prospective clinical study conducted on 21 eyes at 4 sites in Japan. Treatment protocol consisted of two phases. The induction IVR phase included two monthly IVRs followed by PRN IVR phase in which additional IVR was administered if the central macular thickness (CMT) exceeded 300 μm. One week after each IVR in both phases, short pulse focal/grid laser was delivered to treat residual leakage outside of the fovea (>500 μm) and reduce edema fluid influx. At the 6-month endpoint, the effects of treatment were examined in terms of best corrected visual acuity (BCVA), CMT, and required number of IVR injections in eyes with or without perifoveal leaking microaneurysms (MAs).
  
  
  RESULTS
  In eyes with initial BCVA ≤70 letters, mean BCVA was significantly ameliorated by 7.0 ± 7.4 letters (P = 0.0324) and mean CMT improved significantly by 174.8 ± 105.0 µm (P = 0.0005). Both BCVA improvement (P = 0.8693) and CMT reduction (P = 0.9336) were comparable between MA(-) and MA(+) groups. The MA(-) group required significantly fewer PRN-IVR injections than did the MA(+) group over the 6-month study period (mean 3.4 ± 1.6 vs. 5.3 ± 0.9, median 3.0 vs. 5.5; P = 0.0229).
  
  
  CONCLUSIONS
  Short pulse focal/grid laser photocoagulation could reduce the number of IVR injections required to resolve macular edema and increase BCVA in a possible mechanism of reduced influx of edema fluid into the foveal area in eyes without apparent perifoveal microaneurysms.
authors.affiliation: Department of Ophthalmology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Department of Ophthalmology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Toriyama
authors.affiliation: Department of Ophthalmology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Iesato
authors.affiliation: Department of Ophthalmology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Imai
authors.affiliation: Department of Ophthalmology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Hirabayashi
authors.affiliation: Department of Ophthalmology, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido, 078-8510, Japan.
authors.forename: Taiji
authors.initials: T
authors.lastname: Nagaoka
authors.affiliation: Department of Ophthalmology, Faculty of Medical Sciences, University of Fukui, Eiheiji-cho, Yoshida-gun, Fukui-ken, 910-1193, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Takamura
authors.affiliation: Department of Ophthalmology, Mie University School of Medicine, 2-174, Edobashi, Tsu, Mie, 514-8507, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sugimoto
authors.affiliation: Department of Ophthalmology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan. murata@shinshu-u.ac.jp.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Murata
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D003930:Diabetic Retinopathy / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D005584:Fovea Centralis / Q000000981:diagnostic imaging; D006801:Humans; D058449:Intravitreal Injections; D017075:Laser Coagulation / Q000379:methods*; D008269:Macular Edema / Q000150:complications* / Q000175:diagnosis / Q000628:therapy; D008297:Male; D000071071:Microaneurysm / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D008875:Middle Aged; D011446:Prospective Studies; D000069579:Ranibizumab / Q000008:administration & dosage*; D012171:Retinal Vessels / Q000000981:diagnostic imaging / Q000601:surgery; D041623:Tomography, Optical Coherence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D014792:Visual Acuity
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D000069579:Ranibizumab
keywords: Diabetic macular edema; Focal/grid laser photocoagulation; Microaneyrysms; Perifoveal capillary network; Vascular endothelial growth factor