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. 2016 Aug 24;7(1):18.
doi: 10.1186/s13167-016-0066-2. eCollection 2016.

Suppressed endothelin-1 by anti-VEGF therapy is important for patients with BRVO-related macular edema to improve their vision

Teruyo Kida  1 , Josef Flammer  2 , Hidehiro Oku  1 , Seita Morishita  1 , Masanori Fukumoto  1 , Hiroyuki Suzuki  1 , Katarzyna Konieczka  2 , Tsunehiko Ikeda  1
Affiliations

Suppressed endothelin-1 by anti-VEGF therapy is important for patients with BRVO-related macular edema to improve their vision

Teruyo Kida et al. EPMA J. .

Abstract

Background: Branch retinal vein occlusion (BRVO) commonly occurs at the arteriovenous crossing in the unilateral eye, and cardiovascular diseases can be risk factors of BRVO. However, the pathomechanism leading to BRVO is not yet clear. In addition to mechanical compression, the vein might locally constrict due to an altered biochemical environment, such as an increase in the concentration of endothelin-1 (ET-1). We evaluated changes in ET-1 following injection of intravitreal bevacizumab (IVB), which is the anti-vascular endothelial growth factor (VEGF) agent with the longest serum half-life, to determine the effect on BRVO-related macular edema.

Methods: Twenty consecutive patients with BRVO-related macular edema (10 males, 10 females; age range 56-83 years) who visited our hospital were included in this prospective study. Visual acuity (VA); central retinal thickness (CRT), determined by macular optical coherence tomography (OCT); and plasma ET-1 levels were obtained before IVB treatment and 1 month later.

Results: Patients had hypertension (80 %), dyslipidemia (50 %), diabetes mellitus (35 %), or collagen disease (5 %). Mean CRT was significantly decreased from 673.0 ± 327.8 to 388.2 ± 155.0 μm (P = 0.0007), and mean VA was significantly improved after IVB (P = 0.0239). Mean plasma ET-1 was significantly decreased from 1.272 ± 0.451 to 1.095 ± 0.316 pg/mL (P = 0.0238); however, the plasma ET-1 level was increased in all five patients who did not show improved VA after IVB.

Conclusions: In patients with BRVO-related macular edema, anti-VEGF therapy leads to an expected reduction in ET-1 levels; however, the ET-1 level was found to increase in some patients; this is clearly related to less improvement of VA after anti-VEGF therapy.

Trial registration: University hospital Medical Information Network (UMIN) Center UMIN000013236. Registered 10 October, 2012.

Keywords: Anti-VEGF; Branch retinal vein occlusion (BRVO); Endothelin-1; Macular edema.

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Figures

Fig. 1
Fig. 1
A case of 68-year-old female, BRVO with macular edema (patient 2 in Table 1). a Upper: pre-treatment; b lower: 1 month after intravitreal injection of bevacizumab (IVB). Macular edema was dramatically decreased, and the visual acuity was improved from 2/20 to 8/20 1 month after IVB. Plasma ET-1 level was decreased from 1.0567 to 0.568 pg/mL
Fig. 2
Fig. 2
Changes in central retinal thickness (CRT) before and after the treatment. Mean CRT was significantly decreased after the treatment (P = 0.0007, paired t test)
Fig. 3
Fig. 3
A regression line of changes in ET-1 and VA. Before-after change of plasma ET-1 was calculated as follows: (ET-1 level after IVB − ET-1 level before IVB)/ET-1 level before IVB × 100 (%). There was a correlation between changes in ET-1 level and VA before and after IVA (r = 0.638, P = 0.0025)
Fig. 4
Fig. 4
A regression line of changes in CRT and VA in five patients with increased ET-1 after IVB. Before-after change of CRT was calculated as (CRT after IVB − CRT before IVB)/ET-1 level before IVB × 100 (%). There was a correlation between changes in CRT and VA (r = 0.885, P = 0.0478)
Fig. 5
Fig. 5
Before-after changes of plasma endothelin-1 (ET-1) level. Before-after change of plasma ET-1 (%) was calculated as follows: (ET-1 level after IVB − ET-1 level before IVB)/ET-1 level before IVB. Every patient who had visual improvement or maintained VA after anti-VEGF therapy showed significantly decreased plasma ET-1 (*P < 0.0001, unpaired t test)
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