Macular function following intravitreal ranibizumab for macular edema associated with branch retinal vein occlusion

  • Tomoharu Nishimura
  • Shigeki MachidaEmail author
  • Atsushi Tada
  • Eiki Oshida
  • Tetsuya Muto
Original Research Article



To determine the physiology of the macula by the focal macular electroretinograms (fmERGs) in patients with branch retinal vein occlusion with macular edema (BRVOME) treated by intravitreal injections of ranibizumab (IVR).


We studied 17 eyes of 17 patients with BRVOME. The contralateral unaffected eyes served as controls. All patients were treated with an IVR at monthly intervals for 3 consecutive months. The baseline best-corrected visual acuity (BCVA), optical coherence tomographic (OCT) findings, and fmERGs were compared to the post-treatment values. The fmERGs were elicited by a 15° circular spot or a superior or inferior semicircular spot. The center of the spot was placed on the fovea. The amplitudes of the a- and b-waves, photopic negative response (PhNR), and sum of the oscillatory potentials (ΣOPs: sum of OP1, OP2, and OP3 amplitudes) were measured. In addition, the implicit times of the a- and b-waves were also measured.


The BCVA improved significantly from 0.39 ± 0.28 logMAR units to 0.17 ± 0.18 logMAR units after the resolution of the central macular edema (P < 0.01). All components of the fmERGs elicited by the semicircular stimulus spot placed on the occluded side were smaller than that elicited from the corresponding area of the control eyes. The b-wave amplitudes increased significantly from 0.49 ± 0.25 to 0.75 ± 0.36 µV following the IVR injections, but the amplitudes of the a-wave and PhNR remained reduced (P < 0.05). The amplitudes of the PhNR and ΣOPs elicited by stimulating the non-occluded side were reduced with relative preservation of the a- and b-waves (P < 0.05). They recovered after the treatment from 0.27 ± 0.15 to 0.50 ± 0.30 and 0.33 ± 0.15 to 0.53 ± 0.19 µV, respectively.


IVRs improved the macular function not only on the occluded side but also on the non-occluded side. On the occluded side, the BRVOME affects the function of all retinal layers of the macula. Even after the IVR, the function of the photoreceptors and retinal ganglion cells remained abnormal. On the non-occluded side, the inner retinal function improved after the IVR.


Macular function Macular edema BRVO Focal macular ERG Ranibizumab 



Funding/Support: This study was supported by JSPS KAKENHI Grant No. 18K09420 (SM). We thank Dr. Duco Hamasaki for editing the manuscript.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Statement of human rights

This research was conducted in accordance with the Institutional Guidelines of Dokkyo Medical University, and the procedures conformed to the tenets of the Declaration of Helsinki.

Informed consent

An informed consent was obtained from all subjects after a full explanation of the nature of the experiments.

Statement on the welfare of animals

No animals were used in this study.


  1. 1.
    Arakawa S, Yasuda M, Nagata M, Ninomiya T, Hirakawa Y, Doi Y, Kiyohara Y, Ishibashi T (2011) Nine-year incidence and risk factors for retinal vein occlusion in a general Japanese population: the Hisayama study. Invest Ophthalmol Vis Sci 52:5905–5909CrossRefGoogle Scholar
  2. 2.
    Campochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC, Murahashi WY, Rubio RG, Investigators BRAVO (2010) Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology 117:1102–1112CrossRefGoogle Scholar
  3. 3.
    Clark WL, Boyer DS, Heier JS, Brown DM, Haller JA, Vitti R, Kazmi H, Berliner AJ, Erickson K, Chu KW, Soo Y, Cheng Y, Campochiaro PA (2016) Intravitreal aflibercept for macular edema following branch retinal vein occlusion: 52-week results of the VIBRANT study. Ophthalmology 123:330–336CrossRefGoogle Scholar
  4. 4.
    Miyake Y, Yanagida K, Kondo K, Ota I (1981) Subjective scotometry and recording of local electroretinogram and visual evoked response. System with television monitor of the fundus. Jpn J Ophthalmol 25:439–448Google Scholar
  5. 5.
    Miyake Y (1988) Studies on local macular ERG. Acta Soc Ophthalmol Jpn 92:1419–1449Google Scholar
  6. 6.
    Miyake Y (2006) Electrodiagnosis of retinal diseases. Springer, TokyoGoogle Scholar
  7. 7.
    Kondo M, Ueno S, Piao CH, Miyake Y, Terasaki H (2008) Comparison of focal macular cone ERGs in complete-type congenital stationary night blindness and APB-treated monkeys. Vis Res 48:273–280CrossRefGoogle Scholar
  8. 8.
    Miyake Y, Shiroyama N, Ota I, Horiguchi M (1988) Oscillatory potentials in electroretinograms of the human macular region. Invest Ophthalmol Vis Sci 29:1631–1635Google Scholar
  9. 9.
    Miyake Y, Shiroyama N, Horiguchi M, Ota I (1989) Asymmetry of focal ERG in human macular region. Invest Ophthalmol Vis Sci 30:1743–1749Google Scholar
  10. 10.
    Machida S, Toba Y, Ohtaki A, Gotoh Y, Kaneko M, Kurosaka D (2008) Photopic negative response of focal electroretinogram in glaucomatous eyes. Invest Ophthalmol Vis Sci 49:5636–5644CrossRefGoogle Scholar
  11. 11.
    Kondo M, Kurimoto Y, Sakai T, Koyasu T, Miyata K, Ueno S, Terasaki H (2008) Recording focal macular photopic negative response (PhNR) from monkeys. Invest Ophthalmol Vis Sci 49:3544–3550CrossRefGoogle Scholar
  12. 12.
    Hibi N, Ueno S, Ito Y, Piao CH, Kondo M, Terasaki H (2013) Relationship between retinal layer thickness and focal macular electroretinogram components after epiretinal membrane surgery. Invest Ophthalmol Vis Sci 54:7207–7214CrossRefGoogle Scholar
  13. 13.
    Nishimura T, Machida S, Hashizume K, Kurosaka D (2015) Structures affecting recovery of macular function in patients with age-related macular degeneration after intravitreal ranibizumab. Graefes Arch Clin Exp Ophthalmol 253:1201–1209CrossRefGoogle Scholar
  14. 14.
    Nishimura T, Machida S (2018) Correlation between macular structure and function in patients with age-related macular degeneration treated with intravitreal ranibizumab: 12-month-results. Jpn J Ophthalmol. Google Scholar
  15. 15.
    Machida S, Kaneko M, Kurosaka D (2015) Regional variations in correlation between photopic negative response of focal electoretinograms and ganglion cell complex in glaucoma. Curr Eye Res 40:439–449CrossRefGoogle Scholar
  16. 16.
    Ogino K, Tsujikawa A, Murakami T, Muraoka Y, Akagi-Kurashige Y, Ishihara K, Miyamoto K, Nakamura H, Yoshimura N (2011) Evaluation of macular function using focal macular electroretinography in eyes with macular edema associated with branch retinal vein occlusion. Invest Ophthalmol Vis Sci 52:8047–8055CrossRefGoogle Scholar
  17. 17.
    Rishi P, Raka N, Rishi E (2016) Analysis of potential ischemic effect of intravitreal bevacizumab on unaffected retina in treatment-naïve macular edema due to branch retinal vein occlusion: a prospective. Interventional Case-Series. PLoS One 11:e0162533CrossRefGoogle Scholar
  18. 18.
    Kizawa J, Machida S, Kobayashi T, Gotoh Y, Kurosaka D (2006) Changes of oscillatory potentials and photopic negative response in patients with early diabetic retinopathy. Jpn J Ophthalmol 50:367–373CrossRefGoogle Scholar
  19. 19.
    Noma H, Yasuda K, Minezaki T, Watarai S, Shimura M (2016) Changes of retinal flow volume after intravitreal injection of bevacizumab in branch retinal vein occlusion with macular edema: a case series. BMC Ophthalmol 16:61CrossRefGoogle Scholar
  20. 20.
    Samara WA, Shahlaee A, Sridhar J, Khan MA, Ho AC, Hsu J (2016) Quantitative optical coherence tomography angiography features and visual function in eyes with branch retinal vein occlusion. Am J Ophthalmol 166:76–83CrossRefGoogle Scholar
  21. 21.
    Im JC, Shin JP, Kim IT, Park DH (2016) Recurrence of macular edema in eyes with branch retinal vein occlusion changes the diameter of unaffected retinal vessels. Graefes Arch Clin Exp Ophthalmol 254:1267–1274CrossRefGoogle Scholar
  22. 22.
    Yamaike N, Kita M, Tsujikawa A, Miyamoto K, Yoshimura N (2007) Perimetric sensitivity with the micro perimeter 1 and retinal thickness in patients with branch retinal vein occlusion. Am J Ophthalmol 143:342–344CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Tomoharu Nishimura
    • 1
  • Shigeki Machida
    • 1
    Email author
  • Atsushi Tada
    • 1
  • Eiki Oshida
    • 1
  • Tetsuya Muto
    • 1
  1. 1.Department of OphthalmologyDokkyo Medical University Saitama Medical CenterKoshigayaJapan

Personalised recommendations