Applicant: Dr. Tine Van Bergen Promotor: Prof. Dr. Ingeborg Stalmans Aim To compare the effect of aflibercept (VEGF-Trap) to PlGF inhibition on the surgical outcome after glaucoma filtration surgery Material and Methods 1. Introduction We previously showed that inhibition of placental growth factor (PlGF) was more effective than anti- VEGF-R2 treatment in improving surgical ouctome of glaucoma filtration surgery (GFS) (Van Bergen T et al. 2013). In this study, we compared the effect of PlGF inhibition to aflibercept (VEGF-Trap, inhibition of VEGF and PlGF) on surgical outcome after GFS. 2. Study design The effect of PlGF inhibitor (5D11D4; ThromboGenics NV) and aflibercept on surgical outcome was investigated in a mouse model of GFS. The 1st group received an intracameral (IC) injection of 5D11D4 (1 μl; 5.4 μg), while IC administration of aflibercept (1μl; 3.4 μg; Eylea) was given to the 2nd group. The 3rd group was used as positive control and was treated during surgery with MMC 0.02% for 2 minutes. The 2 first groups were also included in combination with MMC 0.02% for 2 minutes. Treatment outcome was studied by clinical investigation of the bleb every other day. Fibrosis was investigated on postoperative day 52 by performing a Sirius Red staining. Conclusion In conclusion, this study indicates that PlGF inhibition is as efficacious as aflibercept, known to inhibit both VEGF and PlGF, in reducing scar formation after GFS. Moreover, PlGF inhibition can enhance the beneficial effects of MMC, which might open new perspectives for the future to investigate whether combination therapy can lower the dose of MMC and anti-PlGF and whether this can improve the safety profile of MMC. PlGF inhibi*on is as eﬃcacious as VEGFTrap in reducing scar forma*on a<er glaucoma surgery Grant 2014 2015: FRO Figure 1 The combination of MMC and 5D11D4 was able to significantly improve bleb area as compared to MMC (n=15; p<0.001; figure 1A-B) by an additional reduction of fibrosis with 10 % at day 52 (n=6; p<0.001; figure 1C). As compared to MMC together with aflibercept (Eylea), the combined administration of MMC and 5D11D4 was equally effective in improving surgical outcome (n=15; p>0.05, figure 1A-B) and reducing the postoperative fibrotic process in the bleb (n=15; p=0.49, figure 2C). Results FONDS VOOR RESEARCH IN OFTALMOLOGIE FONDS POUR LA RECHERCHE EN OPHTALMOLOGIE FUND FOR RESEARCH IN OPHTHALMOLOGY

FONDS POUR LA RECHERCHE EN … 08... · FONDS VOOR RESEARCH IN OFTALMOLOGIE FONDS POUR LA RECHERCHE EN OPHTALMOLOGIE FUND FOR RESEARCH IN OPHTHALMOLOGY. Title: 2015 08 15 FRO OB_tva_vs2.pptx

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Page 1: FONDS POUR LA RECHERCHE EN … 08... · FONDS VOOR RESEARCH IN OFTALMOLOGIE FONDS POUR LA RECHERCHE EN OPHTALMOLOGIE FUND FOR RESEARCH IN OPHTHALMOLOGY. Title: 2015 08 15 FRO OB_tva_vs2.pptx

Applicant: Dr. Tine Van Bergen Promotor: Prof. Dr. Ingeborg Stalmans

Aim

To compare the effect of aflibercept (VEGF-Trap) to PlGF inhibition on the surgical outcome after glaucoma filtration surgery

Material and Methods 1. Introduction We previously showed that inhibition of placental growth factor (PlGF) was more effective than anti-VEGF-R2 treatment in improving surgical ouctome of glaucoma filtration surgery (GFS) (Van Bergen T et al. 2013). In this study, we compared the effect of PlGF inhibition to aflibercept (VEGF-Trap, inhibition of VEGF and PlGF) on surgical outcome after GFS. 2. Study design The effect of PlGF inhibitor (5D11D4; ThromboGenics NV) and aflibercept on surgical outcome was investigated in a mouse model of GFS. The 1st group received an intracameral (IC) injection of 5D11D4 (1 µl; 5.4 µg), while IC administration of aflibercept (1µl; 3.4 µg; Eylea) was given to the 2nd group. The 3rd group was used as positive control and was treated during surgery with MMC 0.02% for 2 minutes. The 2 first groups were also included in combination with MMC 0.02% for 2 minutes. Treatment outcome was studied by clinical investigation of the bleb every other day. Fibrosis was investigated on postoperative day 52 by performing a Sirius Red staining.

Conclusion

In conclusion, this study indicates that PlGF inhibition is as efficacious as aflibercept, known to inhibit both VEGF and PlGF, in reducing scar formation after GFS. Moreover,

PlGF inhibition can enhance the beneficial effects of MMC, which might open new perspectives for the future to investigate whether combination therapy can lower the dose of MMC and anti-PlGF and whether this can improve the safety profile of MMC.

PlGF inhibi*on is as efficacious as VEGF-‐Trap in reducing scar forma*on a<er glaucoma surgery

Grant 2014 -‐2015: FRO

Figure 1 The combination of MMC and 5D11D4 was able to significantly improve bleb area as compared to MMC (n=15; p<0.001; figure 1A-B) by an additional reduction of fibrosis with 10 % at day 52 (n=6; p<0.001; figure 1C). As compared to MMC together with aflibercept (Eylea), the combined administration of MMC and 5D11D4 was equally effective in improving surgical outcome (n=15; p>0.05, figure 1A-B) and reducing the postoperative fibrotic process in the bleb (n=15; p=0.49, figure 2C).

Results

FONDS VOOR RESEARCH IN OFTALMOLOGIEFONDS POUR LA RECHERCHE EN OPHTALMOLOGIE

FUND FOR RESEARCH IN OPHTHALMOLOGY